JP3746563B2 - Pentacyclic compound - Google Patents
Pentacyclic compound Download PDFInfo
- Publication number
- JP3746563B2 JP3746563B2 JP10661596A JP10661596A JP3746563B2 JP 3746563 B2 JP3746563 B2 JP 3746563B2 JP 10661596 A JP10661596 A JP 10661596A JP 10661596 A JP10661596 A JP 10661596A JP 3746563 B2 JP3746563 B2 JP 3746563B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- atom
- tms
- nmr
- ppm
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims description 302
- -1 Group Chemical group 0.000 claims description 146
- 125000000217 alkyl group Chemical group 0.000 claims description 87
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 60
- 125000000623 heterocyclic group Chemical group 0.000 claims description 50
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 125000003342 alkenyl group Chemical group 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 125000003277 amino group Chemical group 0.000 claims description 24
- 125000004429 atom Chemical group 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims description 20
- 239000000470 constituent Substances 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000004423 acyloxy group Chemical group 0.000 claims description 14
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 12
- 125000004434 sulfur atom Chemical group 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 229910052727 yttrium Inorganic materials 0.000 claims description 11
- 125000004442 acylamino group Chemical group 0.000 claims description 10
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 10
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 4
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 claims description 3
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5beta,20-epoxy-1,7beta,13alpha-trihydroxy-9-oxotax-11-ene-2alpha,4alpha,10beta-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 description 273
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 261
- 238000005160 1H NMR spectroscopy Methods 0.000 description 220
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 140
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 138
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 132
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 129
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 123
- 238000002844 melting Methods 0.000 description 122
- 230000008018 melting Effects 0.000 description 122
- 229930014667 baccatin III Natural products 0.000 description 105
- 239000002904 solvent Substances 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 238000006243 chemical reaction Methods 0.000 description 71
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- 239000000203 mixture Substances 0.000 description 58
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 52
- 239000000243 solution Substances 0.000 description 51
- 239000000126 substance Substances 0.000 description 48
- 239000002994 raw material Substances 0.000 description 44
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 41
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 34
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- 229920006395 saturated elastomer Polymers 0.000 description 26
- 238000004809 thin layer chromatography Methods 0.000 description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 25
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 23
- 238000000034 method Methods 0.000 description 23
- 238000010898 silica gel chromatography Methods 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 14
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 12
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 235000019270 ammonium chloride Nutrition 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 238000001035 drying Methods 0.000 description 9
- 239000011521 glass Substances 0.000 description 9
- 239000012046 mixed solvent Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 8
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 8
- 239000006188 syrup Substances 0.000 description 8
- 235000020357 syrup Nutrition 0.000 description 8
- 229930012538 Paclitaxel Natural products 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 229960001592 paclitaxel Drugs 0.000 description 7
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 150000004579 taxol derivatives Chemical class 0.000 description 5
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 description 5
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 4
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 3
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 3
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 3
- 0 CC[C@](C)C(C)=C(C)[C@]1OC(C)(C)O[C@]1[C@](C)[C@@](C)C[C@](C)*C(C)C Chemical compound CC[C@](C)C(C)=C(C)[C@]1OC(C)(C)O[C@]1[C@](C)[C@@](C)C[C@](C)*C(C)C 0.000 description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 3
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 3
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 3
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 3
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 3
- 229930192474 thiophene Natural products 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 2
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- MCIPQLOKVXSHTD-UHFFFAOYSA-N 3,3-diethoxyprop-1-ene Chemical compound CCOC(C=C)OCC MCIPQLOKVXSHTD-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- JHLVEBNWCCKSGY-UHFFFAOYSA-N CC(C)(C)OC(NC)=O Chemical compound CC(C)(C)OC(NC)=O JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- GCSAXWHQFYOIFE-UHFFFAOYSA-N dipyridin-2-yl carbonate Chemical compound C=1C=CC=NC=1OC(=O)OC1=CC=CC=N1 GCSAXWHQFYOIFE-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- SPAKMVQVTSVXES-UHFFFAOYSA-N methanol;oxolane;hydrate Chemical compound O.OC.C1CCOC1 SPAKMVQVTSVXES-UHFFFAOYSA-N 0.000 description 2
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 2
- VZOPRCCTKLAGPN-ZFJVMAEJSA-L potassium;sodium;(2r,3r)-2,3-dihydroxybutanedioate;tetrahydrate Chemical compound O.O.O.O.[Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VZOPRCCTKLAGPN-ZFJVMAEJSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- PHEHAQNGGWXAET-ZWKOTPCHSA-N tert-butyl (2r,3r)-2-(furan-2-yl)-4-oxo-3-tri(propan-2-yl)silyloxyazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(=O)[C@H](O[Si](C(C)C)(C(C)C)C(C)C)[C@@H]1C1=CC=CO1 PHEHAQNGGWXAET-ZWKOTPCHSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- NNHYAHOTXLASEA-UHFFFAOYSA-N 1-(dimethoxymethyl)-4-methoxybenzene Chemical compound COC(OC)C1=CC=C(OC)C=C1 NNHYAHOTXLASEA-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- BBGMYHRHDNBZLZ-UHFFFAOYSA-N 2,2-difluoro-3-(furan-2-yl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(F)(F)C(O)=O)C1=CC=CO1 BBGMYHRHDNBZLZ-UHFFFAOYSA-N 0.000 description 1
- UWKQJZCTQGMHKD-UHFFFAOYSA-N 2,6-di-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=N1 UWKQJZCTQGMHKD-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- OGTYLYWEEJWYIK-NPMSKOETSA-N CC([C@](C)([C@H]1CO)C2=[O]CO[C@@H]2CC(C)(C)CCC[C@H]1OC(c1ccccc1)=O)O Chemical compound CC([C@](C)([C@H]1CO)C2=[O]CO[C@@H]2CC(C)(C)CCC[C@H]1OC(c1ccccc1)=O)O OGTYLYWEEJWYIK-NPMSKOETSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241001116500 Taxus Species 0.000 description 1
- 241001116498 Taxus baccata Species 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- WMKHLIDRGVLCLH-RIFKXWPOSA-N [(1S,2S,3R,4S,7R,10R,12R,15S)-4-acetyloxy-1,12,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)CC[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 WMKHLIDRGVLCLH-RIFKXWPOSA-N 0.000 description 1
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- CPPBMSQAWQOUCQ-UHFFFAOYSA-N acetic acid;1,4-dioxan-2-ylmethanol Chemical compound CC(O)=O.OCC1COCCO1 CPPBMSQAWQOUCQ-UHFFFAOYSA-N 0.000 description 1
- ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- FDJUMMKAFUMWBI-UHFFFAOYSA-N chloro carbonochloridate Chemical compound ClOC(Cl)=O FDJUMMKAFUMWBI-UHFFFAOYSA-N 0.000 description 1
- QABCGOSYZHCPGN-UHFFFAOYSA-N chloro(dimethyl)silicon Chemical compound C[Si](C)Cl QABCGOSYZHCPGN-UHFFFAOYSA-N 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000006317 cyclopropyl amino group Chemical group 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- SYCQBMFPHBTFLK-UHFFFAOYSA-N imidazol-2-ylidenemethanethione Chemical compound S=C=C1N=CC=N1 SYCQBMFPHBTFLK-UHFFFAOYSA-N 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical group [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- LMIWBLPJPQVTDX-UHFFFAOYSA-N tert-butyl 3-[tert-butyl(dimethyl)silyl]oxy-2-oxo-4-phenylazetidine-1-carboxylate Chemical compound CC(C)(C)[Si](C)(C)OC1C(=O)N(C(=O)OC(C)(C)C)C1C1=CC=CC=C1 LMIWBLPJPQVTDX-UHFFFAOYSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【０００１】
【産業上の利用分野】
本発明は抗腫瘍作用を有する新規タキソール誘導体に関するものである。
【０００２】
【従来の技術】
タキソールは化７に示す化学構造式で表される天然物で、西洋イチイの幹などから微量得られる。
【０００３】
【化７】
タキソールは抗腫瘍活性を有することが知られているが、その作用機作は細胞分裂における微小管の解重合阻害作用に基づくものとされており、従来の抗腫瘍剤とは異なるタイプの抗腫瘍剤としてその臨床応用が期待されている。
【０００５】
これまでは、タキソールは天然から極く微量しか得られなかった。しかし、イチイ類の葉等から比較的多量に得ることのできる化８で表されるタキソール前駆体である１０−Ｏ−デアセチルバッカチン III
【０００６】
【化８】
を原料に用いて合成したタキソール誘導体が報告され始めている（特開平０３−５０５７２５号公報参照）。なかでも化９で表される構造を有する化合物（タキソテール）は、タキソールと同等以上の抗腫瘍活性を有する化合物として注目され、現在抗腫瘍剤としての開発が進められている。
【０００８】
【化９】
【発明が解決しようとする課題】
タキソールや化９で表される化合物は抗腫瘍剤として有望なものである。しかしながら、臨床試験で消化器癌、特に大腸癌等に対する有効性は低いことが判明し、より強い抗腫瘍効果を持つ誘導体が望まれている。
【００１０】
【課題を解決するための手段】
通常、タキソール誘導体の９位はケト基であるが、この部分が還元された誘導体もいくつか知られている。９位にα配置の水酸基を有する化合物は天然から得られ、これをさらに化学修飾した９位α水酸基型誘導体が各種報告されている（例えば、Ｊ．Ｍｅｄ．Ｃｈｅｍ．，３７，２６５５（１９９４））。また、９位にβ配置の水酸基を有する化合物は１０−Ｏ−デアセチルバッカチン IIIを還元剤を用いて還元することにより化学的に合成できることが知られており、９位β水酸基型誘導体が各種報告されている（例えば、ＷＯ９４／２００８８）。本発明者等は鋭意検討した結果、９位β水酸基型タキソール誘導体の９位水酸基と１０位の水酸基を環状アセタール型に変換することにより抗腫瘍活性が大幅に上昇することを見いだし、本発明を完成した。
【００１１】
本発明は一般式（Ｉ）
【００１２】
【化１０】
［式中、
Ｒ1 はフェニル基を意味し、該フェニル基はハロゲン原子、アルキル基およびアルコキシル基からなる群から選ばれる基を置換基として１個または複数個有していてもよい。
【００１４】
Ｒ2 はアルキル基、アルケニル基、アルキニル基、シクロアルキル基またはアルコキシル基を意味し、これらアルキル基、アルケニル基、アルキニル基、シクロアルキル基およびアルコキシル基は、ハロゲン原子、水酸基、カルボキシル基、アルコキシル基、アリールオキシ基、フェニル基、アミノ基、アルキルアミノ基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基およびアシルオキシ基からなる群から選ばれる基を置換基として１個または複数個有していてもよい。
【００１５】
Ｒ3 は水素原子、水酸基、ハロゲン原子、アルコキシル基、基−Ｏ−Ｒ31、アシルオキシ基または基−Ｏ−ＣＯ−Ｒ31を意味し、該アルコキシル基およびアシルオキシ基は、ハロゲン原子、水酸基、カルボキシル基、シクロアルキル基、アルコキシル基、アリール基、アリールオキシ基、アミノ基、アルキルアミノ基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基、アシルオキシ基および複素環基（該複素環基は、その環の構成原子上にアルキル基を１個または複数個有してもよい。）からなる群から選ばれる基を置換基として１個または複数個有してもよい。
（ここで、Ｒ31はアルキルアミノ基、アルケニル基、アルキニル基、シクロアルキル基、アリール基または複素環基を意味する。なお、これらアルキルアミノ基、アルケニル基、アルキニル基、シクロアルキル基、アリール基および複素環基は、ハロゲン原子、水酸基、カルボキシル基、アルキル基、アルコキシル基、アリールオキシ基、フェニル基、アミノ基、アルキルアミノ基、アミノアルキル基、アルキルアミノアルキル基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基、アシルオキシ基および３員環から８員環の大きさの含窒素複素環基（該含窒素複素環基は、その環の構成原子上にアルキル基を１個または複数個有してもよい。）からなる群から選ばれる基を置換基として１個または複数個有してもよい。）
また、Ｒ3 はこれが結合している炭素原子に隣接する炭素原子に結合しているメチル基と共に３員環を形成してもよい。
【００１６】
Ｒ4 およびＲ5 は各々独立して、水素原子、アルキル基、アルケニル基、アルキニル基、アリール基または複素環基を意味し、これらアルキル基、アルケニル基、アルキニル基、アリール基および複素環基は、アルコキシル基、アミノ基、アルキルアミノ基、アミノアルキル基、アルキルアミノアルキル基および式
【００１７】
【化１１】
で表される、窒素原子を含む５員環から６員環の大きさの飽和の複素環基（該複素環基は、その環の構成原子である炭素原子上にアルキル基を有してもよい。）からなる群から選ばれる基を置換基として有してもよい。
【００１８】
Ｚ1 は水素原子、水酸基、ハロゲン原子またはアルキル基を意味し、
Ｚ2 は水素原子、水酸基、ハロゲン原子またはアルキル基を意味し、
Ｚ3 はアルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基または複素環基を意味し、これらアルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基および複素環基は、ハロゲン原子、水酸基、カルボキシル基、アルキル基、アルコキシル基、フェニル基、アミノ基、アルキルアミノ基、アミノアルキル基、アルキルアミノアルキル基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基およびアシルオキシ基からなる群から選ばれる基を置換基として１個または複数個有してもよい。
【００１９】
Ｚ4 はアルキル基、アリール基またはアルコキシル基を意味し、これらアルキル基、アリール基およびアルコキシル基は、ハロゲン原子、水酸基、カルボキシル基、アルキル基、アルコキシル基、フェニル基、アミノ基、アルキルアミノ基、アミノアルキル基、アルキルアミノアルキル基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基およびアシルオキシ基からなる群から選ばれる基を置換基として１個または複数個有してもよい。
【００２０】
なお、
【００２１】
【化１２】
で表される化合物およびその塩に関する。
【００２２】
また、本発明は一般式（Ｉａ）
【００２３】
【化１３】
で表される立体配置を有する化合物およびその塩に関する。
【００２４】
次に、本明細書で用いる用語について説明する。
【００２５】
ここで用いられる、“Ｃ1 〜Ｃ6 ”とは炭素数１から６のものという意味で、例えば、“Ｃ2 〜Ｃ6 アルケニル基”は炭素数が２から６のアルケニル基を意味する。
【００２６】
“アルキル基”、“アルケニル基”および“アルキニル基”は直鎖でも分枝鎖でもよく、炭素数１（アルケニル基およびアルキニル基の場合は炭素数２）から炭素数６までのものが好ましい。
【００２７】
“アルコキシル基”とは、基−Ｏ−にアルキル基が結合したものを意味するが、該アルキル基にフェニル基（置換基を有していてもよい。）が置換してもよく、この様な例としてはベンジルオキシ、フェネチルオキシ、ｐ−メトキシベンジルオキシ等が挙げられる。なお、アルキル部分は炭素数１から６のものが好ましい。
【００２８】
“アルコキシカルボニル基”とは、基−ＣＯＯ−の酸素原子にアルキル基が結合したものを意味するが、該アルキル基にフェニル基（置換基を有していてもよい。）が置換してもよく、この様な例としては、ベンジルオキシカルボニル、フェネチルオキシカルボニル、ｐ−メトキシベンジルオキシカルボニル等が挙げられる。なお、アルキル部分は炭素数１から６のものが好ましい。
【００２９】
“アリール基”とは、芳香族炭化水素の核から水素原子１個を除いた１価基のことを意味し、例えば、フェニル、トリル、ビフェニリル、ナフチル等が挙げられる。
【００３０】
“アミノアルキル基”のアミノ基の結合位置はアルキル基のどの位置でもよい。また、アルキル基の炭素数は１から６が好ましい。
【００３１】
“アルキルアミノ基”とは、アミノ基にアルキル基が１個置換したもの、あるいはアミノ基にアルキル基が２個置換したもの（２個のアルキル基は同一でも異なっても良い。）を意味する。また、アルキル基の炭素数は１から６が好ましい。
【００３２】
“アシル基”とは、カルボニル基（−ＣＯ−）に水素原子、アルキル基またはアリール基が結合したものを意味し、例えば、ホルミル、アセチル、プロパノイル、ベンゾイル等が挙げられる。なお結合するアルキル基としては、炭素数１から６のものが好ましく、結合するアリール基としてはフェニル基が好ましい。
【００３３】
“複素環基”とは、環構造の構成原子として酸素原子、窒素原子および硫黄原子からなる群から選ばれる原子の１種以上を１個または複数個含む、単環性あるいは二環性の飽和もしくは不飽和の複素環化合物から導かれる置換基を意味し、これら複素環基はいずれの位置で結合してもよい。単環性の複素環基としては、例えば、ピロール、フラン、チオフェン、ピロリジン、テトラヒドロフラン、テトラヒドロチオフェン、イミダゾール、ピラゾール、イミダゾリジン、ピラゾリジン、オキサゾール、チアゾール、オキサジアゾール、チアジアゾール、ピリジン、ジヒドロピリジン、テトラヒドロピラン、ピペリジン、ピリダジン、ピリミジン、ピラジン、ピペラジン、ジオキサン、ピラン、モルホリン等の単環性の複素環化合物から導かれる置換基が挙げられる。二環性の複素環基としては、ベンゾフラン、インドリジン、ベンゾチオフェン、インドール、ナフチリジン、キノキサリン、キナゾリン、クロマン等の二環性の複素環化合物から導かれる置換基が挙げられる。
【００３４】
“含窒素複素環基”とは、複素環基の構成原子として必ず窒素原子を１個含み、他に構成原子として酸素原子、窒素原子および硫黄原子からなる群から選ばれる原子の１種以上を１個または複数個含むこともある飽和または不飽和の複素環化合物から導かれる置換基を意味する。例えば、ピロール、ピロリジン、イミダゾール、ピラゾール、イミダゾリジン、ピラゾリジン、オキサゾール、チアゾール、オキサジアゾール、チアジアゾール、ピリジン、ジヒドロピリジン、ピペリジン、ピリダジン、ピリミジン、ピラジン、ピペラジン、モルホリン、チオモルホリン等が挙げられる。
【００３５】
“式
【００３６】
【化１４】
（Ｘは酸素原子、硫黄原子、ＣＨ２、ＣＨ−Ｙ、ＮＨまたはＮ−Ｙを意味し、Ｙはアルキル基を意味する。）
で表される、窒素原子を含む５員環から６員環の大きさの飽和の複素環基（該複素環基は、その環の構成原子である炭素原子上にアルキル基を１個または複数個有してもよい。）”とは、複素環基の構成原子として必ず窒素原子を１個含む５員環から６員環の大きさの飽和の複素環化合物から導かれる置換基を意味し、例えば、ピロリジン、イミダゾリジン、ピラゾリジン、オキサゾリジン、チアゾリジン、イソオキサゾリジン、イソチアゾリジン、ピペリジン、ピペラジン、モルホリン、チオモルホリン等が挙げられる。
【００３８】
Ｒ3 が、Ｒ3 が結合している炭素原子の隣の炭素原子に結合しているメチル基と共に３員環を形成するとは、７位および８位部分が次の構造となること意味している。
【００３９】
【化１５】
次に、一般式（Ｉ）中の各置換基について説明する。
【００４１】
Ｒ1 のフェニル基の置換基としての“アルキル基”、“アルコキシル基”は炭素数１から３のものが好ましい。
【００４２】
Ｒ1 のフェニル基の置換基の数としては、１または２が好ましく、置換基の置換位置は、メタ位が好ましい。
【００４３】
Ｒ1 としては、無置換のフェニル基が好ましい。また、フッ素原子、塩素原子、メチル基もしくはメトキシ基が１個または２個メタ位に置換したフェニル基も好ましいものとして挙げられる。
【００４４】
Ｒ2 としては、アルキル基、アルコキシル基およびシクロアルキル基が好ましい。
【００４５】
Ｒ2 の“アルキル基”としては、Ｃ1 〜Ｃ6 アルキル基が好ましく、特にメチル基、エチル基、プロピル基が好ましい。
【００４６】
Ｒ2 の“アルコキシル基”としては、Ｃ1 〜Ｃ6 アルコキシル基が好ましく、特にメトキシ基、エトキシ基が好ましい。
【００４７】
Ｒ2 の“シクロアルキル基”としては、Ｃ3 〜Ｃ6 シクロアルキル基が好ましく、特にシクロプロピル基が好ましい。
【００４８】
Ｒ2 としては、メチル基、エチル基、プロピル基、メトキシ基、エトキシ基またはシクロプロピル基が特に好ましい。
【００４９】
Ｒ3 の“ハロゲン原子”としては、フッ素原子が好ましい。
【００５０】
Ｒ3 としては水素原子、フッ素原子または水酸基が特に好ましい。また、Ｒ3 としてはＲ3 が結合している炭素原子（７位）の隣の炭素原子（８位）に結合しているメチル基と共に３員環を形成したもの、すなわち７位および８位部分が次の構造となったものも好ましい例として挙げられる。
【００５１】
【化１６】
Ｒ4 およびＲ5 のアルキル基は炭素数１から６のものが好ましく、特にメチル基、エチル基、プロピル基が好ましい。
【００５３】
Ｒ4 およびＲ5 のアルケニル基としては、炭素数２から６のものが好ましく、特にアリル基が好ましい。
【００５４】
Ｒ4 およびＲ5 のアルキル基、アルケニル基またはフェニル基の置換基としては、アミノ基、アルキルアミノ基、または式
【００５５】
【化１７】
で表される、窒素原子を含む５員環または６員環の大きさの飽和の複素環基（該複素環基は、その環の構成原子である炭素原子上にアルキル基を有してもよい。）が好ましい。
【００５６】
アルキルアミノ基のアルキル部分はＣ1 〜Ｃ3 アルキル基が好ましく、ジアルキル置換でもよい。（ジアルキル置換の場合、その２つのアルキル基は同一でも異なっていてもよい。）
なお、式
【００５７】
【化１８】
【００５８】
また、複素環基の環の構成原子である炭素原子上に置換するアルキル基としては、メチル基が好ましい。
【００５９】
Ｒ4 およびＲ5 として好ましいのは、他方が水素原子またはアルキル基で、もう一方がアルキル基、アルケニル基またはフェニル基である組み合わせが挙げられる。
【００６０】
Ｚ1 およびＺ2 の“ハロゲン原子”としては、フッ素原子、塩素原子および臭素原子が好ましい。
【００６１】
Ｚ1 およびＺ2 の“アルキル基”としては、メチル基、エチル基、プロピル基が好ましい。
【００６２】
Ｚ1 としては、ハロゲン原子、水酸基が好ましく、ハロゲン原子の中では、特にフッ素原子が好ましい。
【００６３】
Ｚ2 としては、ハロゲン原子、水素原子またはアルキル基が好ましい。ハロゲン原子の中では、特にフッ素原子が好ましい。アルキル基の中では、特にメチル基が好ましい。
【００６４】
Ｚ1 およびＺ2 として最も好ましいのは、Ｚ1 がフッ素原子、Ｚ2 がフッ素原子の組み合わせのもの、Ｚ1 が水酸基、Ｚ2 が水素原子の組み合わせのもの、あるいはＺ1 が水酸基、Ｚ2 がメチル基の組み合わせのものが挙げられる。
【００６５】
Ｚ3 としてはアリール基、複素環基、アルケニル基が好ましい。
【００６６】
Ｚ3 の“アリール基”としては、フェニル基が好ましい。
【００６７】
Ｚ3 の“アルケニル基”としては、２−メチル−１−プロペニルが好ましい。
【００６８】
Ｚ3 の複素環基としては、単環性の複素環基が好ましく、さらには、単環性の５員環または６員環の複素環基が好ましく、例えば、ピロール、フラン、チオフェン、ピロリジン、テトラヒドロフラン、テトラヒドロチオフェン、イミダゾール、ピラゾール、イミダゾリジン、ピラゾリジン、オキサゾール、チアゾール、オキサジアゾール、チアジアゾール、ピリジン、ジヒドロピリジン、テトラヒドロピラン、ピペリジン、ピリダジン、ピリミジン、ピラジン、ピペラジン、ジオキサン、ピラン、モルホリン等が挙げられる。
【００６９】
Ｚ3 の複素環基の中では、単環性の５員環または６員環の複素環基で環構造の構成原子として酸素原子、窒素原子または硫黄原子を１個含む複素環基が特に好ましく、例えば、ピロール、フラン、チオフェン、ピロリジン、テトラヒドロフラン、テトラヒドロチオフェン、ピリジン、ジヒドロピリジン、テトラヒドロピラン、ピペリジン、ピラン等から導かれる基が挙げられる。
【００７０】
Ｚ3 の複素環基の中では、単環性の５員環または６員環の複素環基で環構造の構成原子として酸素原子、窒素原子または硫黄原子を１個含む不飽和の複素環基が最も好ましいものとして挙げられ、具体的には、フラン、ピリジン、ピロールから導かれる基が最も好ましい。
【００７１】
Ｚ3 としては、２−メチル−１−プロペニル基、フェニル基、フリル基、ピリジル基、ピロリル基が特に好ましい。
【００７２】
Ｚ4 はアリール基またはアルコキシル基が好ましい。
【００７３】
Ｚ4 の“アリール基”としては、フェニル基が好ましい。
【００７４】
Ｚ4 の“アルコキシル基”としては、第三級ブトキシが好ましい。
【００７５】
Ｚ4 としては、フェニル基、第三級ブトキシ基が特に好ましい。
【００７６】
本発明においては、化１９に示す立体配置のものが好ましい。
【００７７】
【化１９】
置換基Ｚ3 の結合している３' 位の立体配置は、どちらの立体配置のものも含まれるが、天然のタキソールと同じ立体配置のものがより好ましい。また、７位の立体配置はα、βどちらの配置のものも含まれる。
【００７９】
本発明のタキソール誘導体は遊離体のままでもよいが、酸付加塩としてあるいはカルボキシル基の塩としてもよい。酸付加塩とする場合の例としては、塩酸塩、硫酸塩、硝酸塩、臭化水素酸塩、ヨウ化水素酸塩、リン酸塩等の無機酸塩類、あるいは酢酸塩、メタンスルホン酸塩、ベンゼンスルホン酸塩、トルエンスルホン酸塩、クエン酸塩、マレイン酸塩、フマル酸塩、乳酸塩等の有機酸塩類を挙げることができる。
【００８０】
また、カルボキシル基の塩としては、例えばリチウム塩、ナトリウム塩、カリウム塩等のアルカリ金属塩、マグネシウム塩、カルシウム塩等のアルカリ土類金属塩、アンモニウム塩、またトリエチルアミン塩やＮ−メチルグルカミン塩、トリス−（ヒドロキシルメチル）アミノメタン塩等で無機塩類、有機塩類の何れでもよい。
【００８１】
本発明化合物の製造法を説明する。なお、反応に際しては、必要に応じて置換基を保護基で保護して行ない、各置換基の変換順序は、特に限定されない。
【００８２】
【化２０】
【化２１】
Ｒ13はＲ3 であるか、または保護基によって保護されているＲ3 （Ｒ3 が水酸基またはアミノ基などで置換されている場合あるいはＲ3 が水酸基の場合）を意味する。
Ｒ14はＲ4 であるか、または保護基によって保護されているＲ4 （Ｒ4 がアミノ基などで置換されている場合）を意味する。
Ｒ15はＲ5 であるか、または保護基によって保護されているＲ5 （Ｒ5 がアミノ基などで置換されている場合）を意味する。
Ｚ11はＺ1 であるか、または保護基によって保護されているＺ1 （Ｚ1 が水酸基の場合）を意味する。
Ｚ21はＺ2 であるか、または保護基によって保護されているＺ2 （Ｚ2 が水酸基の場合）を意味する。
Ｚ31はＺ3 であるか、または保護基によって保護されているＺ3 （Ｚ3 が水酸基またはアミノ基などで置換されている場合）を意味する。
Ｚ41はＺ4 であるか、または保護基によって保護されているＺ4 （Ｚ4 が水酸基またはアミノ基などで置換されている場合）を意味する。
Ｒ8 およびＲ9 はそれぞれ独立して水素原子、アルキル基、アリール基等を意味し、両方ともメチル基であるものや一方がｐ−メトキシフェニル基で他方が水素原子であるものが好ましい。
Ｒ10およびＲ11は水酸基の保護基を表す。
【００８５】
１０−Ｏ−デアセチルバッカチン III（▲１▼）から誘導できる化合物▲２▼と、Ｒ14Ｃ（＝Ｏ）Ｒ15で表されるアルデヒドまたはケトン、あるいはＲ14Ｒ15Ｃ（ＯＲ45）2 で表される（Ｒ45はメチル基などのアルキル基を表す。）アセタールを１０−カンファースルホン酸やｐ−トルエンスルホン酸などの酸性触媒存在下で反応させることにより化合物▲３▼を得ることができる。続いて、化合物▲３▼の１３位の水酸基に化合物（Ａ），（Ｂ）または（Ｃ）を文献上報告されている方法で縮合させることにより化合物▲４▼を得ることができる。
【００８６】
化合物（Ａ）または（Ｂ）を用いる縮合反応としては、４−ジメチルアミノピリジン等の塩基触媒の存在下、ジ（２−ピリジル）カルボネートやジシクロヘキシルカルボジイミドのようなカルボン酸の活性化剤を用いる方法が知られている。なお、化合物（Ａ）を用いた場合は、Ｚ11およびＺ21は水素原子と水酸基の組み合わせとなる。
【００８７】
化合物（Ｃ）を用いる縮合反応としては、ナトリウムヘキサメチルジシラジド等の塩基を用いる方法が知られている。
【００８８】
この時、化合物▲３▼の７位の水酸基に化合物（Ａ），（Ｂ）または（Ｃ）が反応する場合もあるが、その場合にはシリカゲルカラムクロマトグラフィー等の方法で分離精製すればよいが、保護基の種類と反応条件を適切に選択することにより化合物▲３▼の７位に選択的に保護基を導入した化合物▲５▼を得ることができ（特にカルバメート型保護基の場合に高い選択性が得られ、例えば、ピリジン中０℃冷却下で２，２，２−トリクロロエトキシカルボニルクロリドを反応させることにより、７位を選択的に２，２，２−トリクロロエトキシカルボニル基で保護することができる。）、この化合物▲５▼の１３位の水酸基に化合物（Ａ），（Ｂ）または（Ｃ）を上記と同様の方法で縮合させ化合物▲４▼を合成してもよい。また、化合物▲３▼の１３位の水酸基を二酸化マンガン等の酸化剤でケトンに変換した後、７位の水酸基に保護基を導入して化合物▲６▼を合成し、再び水素化ホウ素ナトリウム等の還元剤を用いて１３位のケトンを水酸基に還元して化合物▲５▼を得る方法もある。
【００８９】
こうして得られた化合物▲４▼の各置換基を必要に応じて変換したり脱保護して、２位のベンゾイル基をＣＯＲ1 に、４位のアセチル基をＣＯＲ2 に、７位の水酸基をＲ3 に、Ｒ14，Ｒ15，Ｚ11，Ｚ21，Ｚ31およびＺ41をそれぞれＲ4 ，Ｒ5 ，Ｚ1 ，Ｚ2 ，Ｚ3 およびＺ4 に変換して目的とする化合物（Ｉ）を得ることができる。これらの変換および脱保護は通常の有機化学的方法を用いて行うことができるが、以下に例を挙げる。
【００９０】
２位のベンゾイル基をＣＯＲ1 に変換する方法としては、例えば、文献（Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔ．，３５，８９３１（１９９４））記載の方法に従って２位のエステル結合を選択的に加水分解した後、アシル化する方法があり、Ｒ1 がフェニル基以外の化合物を得ることができる。
【００９１】
４位のアセチル基をＣＯＲ2 に変換する方法としては、ナトリウムヘキサメチルジシラジド等の塩基の存在下Ｒ21−Ｘ（Ｒ21はアルキル基、アルケニル基、アリール基を意味し、Ｘはヨウ素原子、臭素原子などのハロゲンル原子、あるいはメタンスルホニル基やパラトルエンスルホニル基などの脱離基を意味する）で表される化合物と−１００℃から室温で反応させる方法があり、Ｒ2 がメチル基以外の化合物を得ることができる。
【００９２】
また、化合物▲６▼をナトリウムヘキサメチルジシラジド等の塩基の存在下Ｒ21−Ｘで表される化合物と反応させることにより４位のアセチル基をＣＯＲ2 に変換した化合物を得、続いて１３位の水酸基を還元し、続いて（Ａ），（Ｂ）または（Ｃ）と縮合することにより、Ｒ2 がメチル基以外の化合物を得ることができる。
【００９３】
７位の水酸基をＲ3 に変換する方法としては、Ｒ3 のタイプにより種々の方法がある。７位の水酸基を文献上知られている方法（例えば、Ｊ．Ｏｒｇ． Ｃｈｅｍ．，５８，５０２８（１９９３））で除去することによりＲ3 が水素である化合物を得ることができる。７位の水酸基を通常の有機化学的方法でカルボン酸または酸クロリドを用いてアシル化することにより、Ｒ3 が−ＯＣ（＝Ｏ）Ｒ31である化合物を得ることができる。７位の水酸基にＣｌＣ（＝Ｏ）ＯＲ32（Ｒ32はパラニトロフェニル基などのアリール基）で表される化合物を反応させた後アミンを反応させる方法、アミンの存在下ホスゲンを作用させる方法、ＣｌＣ（＝Ｏ）ＮＱ1 Ｑ2 （Ｑ1 およびＱ2 はそれぞれ独立して、水素原子またはアルキル基を意味する。）で表される化合物を作用させる方法、あるいはＲ31Ｎ＝Ｃ＝Ｏで表されるイソシアネートを反応させる方法などで、Ｒ3 が−ＯＣ（＝Ｏ）ＮＱ1 Ｑ2 （Ｑ1 およびＱ2 はそれぞれ独立して、水素原子またはアルキル基を意味する。）である化合物を得ることができる。また７位の水酸基を変換した後さらに数工程の有機化学的変換を実施して目的とするＲ3 に変換することもできる。
【００９４】
また、化合物▲５▼の１３位の水酸基を保護基Ｒ10と区別できる保護基Ｒ11で保護した後、Ｒ10を除去して化合物▲８▼を得、化合物▲８▼の７位の水酸基を上記と同様の方法でＲ13 に変換した後、保護基Ｒ11を除去して化合物▲９▼を得ることができる。続いて、化合物▲９▼の１３位の水酸基に化合物（Ａ），（Ｂ）または（Ｃ）を縮合させ、最後に各種置換基の変換や脱保護を実施して目的とする化合物（Ｉ）を得ることができる。なお、化合物▲８▼は保護基Ｒ11や反応条件を適切に選択することにより化合物▲３▼から直接合成することもでき、化合物▲９▼も７位の水酸基の変換により化合物▲３▼から直接合成することができる。
【００９５】
Ｒ3 がハロゲン原子である目的化合物、例えば、Ｒ3 がフッ素原子である化合物は、７位が水酸基である化合物をテトラヒドロフラン、メチレンクロリド、エチルエーテル、トルエン、１，１−ジメトキシエタン等またはこれらの混合溶媒中でジエチルアミノスルファートリフルオライドで処理することにより得ることができる。
【００９６】
化合物▲８▼は、化合物▲１▼から得られる化合物（Ｄ）からも合成できる。化合物（Ｄ）の１３位の水酸基に２，２，２−トリクロロエトキシカルボニル基と区別できる保護基Ｒ11を導入後、７位と１０位の２，２，２−トリクロロエトキシカルボニル基を除去して得られる化合物をテトラブチルアンモニウムボロヒドリド等の還元剤で処理することにより、９位のケトンを水酸基に変換し、その後、上記と同様の方法でアルデヒド、ケトンあるいはアセタールと反応させて、化合物▲８▼を得ることができる。
【００９７】
製造原料である以下の化合物は報告されている方法で合成できる。
化合物▲２▼ ＷＯ 94/20088等
化合物（Ｄ） テトラヘドロン, 42, 4451 (1986)等
化合物（Ａ） テトラヘドロン レター， 33, 5185 (1992)等
化合物（Ｂ） ジャーナル アメリカン ケミカル ソサエティー,
110, 5917 (1988) 等
化合物（Ｃ） テトラヘドロン レター, 34, 4149 (1993)等
上記の合成法では通常は７位がβ配置の化合物が得られるが、９位がケト基で７位が保護されていないタキソール誘導体を塩基で処理すると７位水酸基の立体配置がβからαへ異性化することが知られており、異性化してから９位のケト基を水酸基に還元すれば７位がα配置の化合物を合成できる。
【００９８】
本発明化合物は、例えば、肺癌、消化器癌、卵巣癌、子宮癌、乳癌、肝癌、頭頚部癌、血液癌、腎癌、睾丸腫瘍等の各種癌の治療に用いることができる。
【００９９】
本発明化合物は、静脈内注射、筋肉内注射、皮下注射等の各種注射剤として、あるいは経口投与、経皮投与等の種々の方法によって投与することができる。これらの投与法の中では水性製剤による静脈内投与、及び経口投与が好ましい。水性製剤は薬理学的に許容される酸と酸付加物を形成させるか、ナトリウム等のアルカリ金属塩とすることで調製できる。経口投与の場合では遊離体のままでも、塩の型のいずれでも良い。
【０１００】
製剤の調製方法としては投与法に応じ適当な製剤を選択し、通常用いられている各種製剤の調製法にて調製できる。本発明の抗腫瘍剤の剤型のうち経口用製剤としては例えば錠剤、散剤、顆粒剤、カプセル剤や、溶液剤、シロップ剤、エリキシル剤、油性ないし水性の懸濁液等を例示できる。注射剤の場合は製剤中に安定剤、防腐剤、溶解補助剤等を使用することもできる。これらの補助剤等を含むこともある溶液を容器に収納後、凍結乾燥等によって固形製剤として用時調製の製剤としても良い。
【０１０１】
液体製剤としては、溶液、懸濁剤、乳液剤等を挙げることができるが、これらの製剤を調製する際、添加剤として懸濁剤、乳化剤等を使用することもできる。
【０１０２】
本発明化合物は、哺乳類、特にヒトの癌治療に用いることができ、ヒトに投与する場合、１日あたり１回投与し、適当な間隔で繰り返すのが好ましい。
【０１０３】
投与量としては、体表面積１ｍ2につき約０．５ｍｇから５０ｍｇ、好ましくは約１ｍｇから２０ｍｇの範囲で投与するのが望ましい。
【０１０４】
次に実施例で詳しく説明する。
【０１０５】
【実施例】
実施例１
【０１０６】
【化２２】
工程１：９β-10-デアセチル-9−ジヒドロバッカチン III
10−デアセチルバッカチン III 6.98 g を乾燥した塩化メチレン 200 ml と 1,4−ジオキサン 200 ml を混合させた溶液に溶解させ、室温でテトラブチルアンモニウムボロヒドリド 12.89 gを添加し、そのままの温度で 19 時間撹拌した。反応液を 0℃に冷却し、1 規定塩酸を徐々に滴下して中和した。これを減圧濃縮し、有機溶媒の大部分を留去した。酢酸エチルと水を加えて震盪して有機層を分離し、水層を酢酸エチルで抽出した。全有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；クロロホルム：アセトン＝５：１(v/v) ）で精製し、標記化合物 4.794 gを白色固体として得た。
【０１０８】
Rf=0.65 ( クロロホルム: メタノール＝7:1(v/v))
FAB Mass : 546(M+).
【０１０９】
工程２：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程１で得た化合物 0.4825 g を乾燥した塩化メチレン 4.8 ml と 1,4−ジオキサン 4.8 ml に溶解させ、室温にて 2,2−ジメトキシプロパン 0.54 mlおよびカンファースルホン酸 19.9 mgを添加し、1 時間放置した。0 ℃に冷却しトリエチルアミンを加えて pH=7 とし、溶媒を減圧留去した。得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；クロロホルム：アセトン＝５：１(v/v) ）で精製し、標記化合物 0.2949 g を白色固体として得た。
【０１１０】
Rf=0.36 ( クロロホルム: アセトン＝6:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.16(3H,s), 1.41(3H,s), 1.57(3H,s), 1.63(3H,s), 1.64(3H,s),
1.70-2.20(4H,m), 3.04(1H,d,J=4.9Hz), 3.85(1H,d,J=7.3Hz),
4.04(1H,br-d), 4.33(1H,d,J=8.3Hz), 4.39(1H,d,J=8.3Hz),
4.67(1H,d,J=7.8Hz), 4.80(1H,br), 5.06(1H,s), 5.58(1H,d,J=7.3Hz),
6.02(1H,d,J=4.9Hz), 7.49(2H,t,J=7.3Hz), 7.59(1H,t,J=7.3Hz),
8.13(2H,d,J=7.3Hz).
【０１１１】
工程３：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-( トリイソプロピルシリルオキシ) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程２で得た化合物 49.8 mgと (3R,4R)-1-(tert−ブトキシカルボニル)-4-(2−フリル)-3-( トリイソプロピルシリルオキシ) アゼチジン-2−オン 49.0 mgを乾燥したテトラヒドロフラン 3.4 ml に溶解させ、-58 ℃で 1.0規定ナトリウムヘキサメチルジシラジド（テトラヒドロフラン溶液）を滴下した。30分後、-50 ℃で飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝４：１(v/v) ）で精製し、標記化合物 15.6 mgを無色透明シロップ状の物質として得た。
【０１１２】
Rf=0.09 ( ヘキサン：酢酸エチル＝４：１(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.91-1.02(22H,m), 1.06(3H,s), 1.30(3H,s), 1.39(9H,s), 1.58(3H,s),
1.67(3H,s), 1.68(3H,s), 1.76(3H,s), 1.87(1H,br-s), 2.15-2.23(2H,m),
2.26-2.39(2H,m), 2.45(3H,s), 2.97(1H,d,J=4.9Hz), 3.89(1H,d,J=7.3Hz),
4.01-4.09(1H,m), 4.31(1H,d,J=8.3Hz), 4.39(1H,d,J=8.3Hz),
4.68(1H,br-d,J=6.8Hz), 4.99(1H,s), 5.12(1H,s), 5.23-5.34(2H,m),
5.53(1H,d,J=7.3Hz), 6.02(1H,d,J=4.9Hz), 6.10(1H,br-t,J=8.0Hz),
6.25(1H,d,J=3.4Hz), 6.34(1H,dd,J=3.4Hz,1.9Hz), 7.37(1H,d,J=1.9Hz),
7.48(2H,t,J=7.3Hz), 7.59(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
【０１１３】
工程４：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-ヒドロキシプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程３で得た化合物 44.3 mgを乾燥したピリジン 2.21 mlに溶解させ、0 ℃でフッ化水素−ピリジン 0.44 mlを添加し、室温に戻して14時間撹拌した。0 ℃で冷却した水を加え、酢酸エチルで抽出した。有機層を１規定塩酸、飽和重曹水、飽和食塩水の順で洗浄して無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：アセトン＝６：１(v/v) ）で精製し、標記化合物 33.9 mgを無色透明シロップ状の物質として得た。
【０１１４】
Rf=0.32 ( クロロホルム: アセトン＝6:1(v/v))
融点: 133-135 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.08(3H,s), 1.28(3H,s), 1.41(9H,s), 1.58(3H,s), 1.65(3H,s),
1.67(3H,s), 1.70(3H,s), 1.83-1.94(1H,m), 2.07-2.27(2H,m),
2.36(3H,s), 2.29-2.47(1H,m), 2.94(1H,d,J=4.9Hz), 3.83(1H,d,J=7.3Hz),
4.32(1H,d,J=8.7Hz), 4.39(1H,d,J=8.7Hz), 4.65-4.76(2H,m), 5.10(1H,s),
5.30-5.42(2H,m), 5.54(1H,d,J=7.3Hz), 6.05(1H,d,J=4.9Hz),
6.11(1H,d,J=3.5Hz), 6.36(1H,dd,J=3.5Hz,1.4Hz), 7.39(1H,d,J=1.4Hz),
7.48(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz), 8.11(2H,d,J=7.3Hz).
FAB Mass : 840(MH+).
【０１１５】
実施例２
【０１１６】
【化２３】
工程１：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ-(4-メトキシベンジリデン) バッカチン III
実施例１の工程１で得た化合物を、2,2-ジメトキシプロパンの代わりに4-メトキシベンズアルデヒドジメチルアセタールを使用して、実施例１の工程２と同様に反応させることにより、標記化合物を無色透明シロップ状の物質として得た。
【０１１８】
Rf=0.24 ( クロロホルム: アセトン＝10:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.19(3H,s), 1.50(3H,s), 1.61(3H,s), 1.98(3H,s), 1.96-2.43(m),
2.34(3H,s), 3.10(1H,d,J=4.9Hz), 3.84(3H,s), 3.98(1H,d,J=7.3Hz),
4.09-4.19(1H,m), 4.31(1H,d,J=8.3Hz), 4.39(1H,d,J=8.3Hz),
4.57(1H,d,J=7.8Hz), 4.84(1H,q,J=7.2Hz), 5.07(1H,s),
5.47(1H,d,J=7.3Hz), 5.80(1H,s), 6.04(1H,d,J=4.9Hz),
6.93(2H,d,J=8.8Hz), 7.42-7.55(4H,m), 7.60(1H,t,J=7.4Hz),
8.12(2H,d,J=7.4Hz).
【０１１９】
工程２：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-( トリイソプロピルシリルオキシ) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(4-メトキシベンジリデン) バッカチン III
上記工程１で得た化合物を原料に用い、実施例１の工程３と同様に (3R,4R)-1-(tert−ブトキシカルボニル)-4-(2−フリル)-3-( トリイソプロピルシリルオキシ) アゼチジン-2−オンとの反応操作を行うことにより、標記化合物を無色透明シロップ状の物質として得た。
【０１２０】
Rf=0.28 ( ヘキサン：酢酸エチル＝5:2(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.91-1.08(21H,m), 1.32(3H,s), 1.54(3H,s), 1.72(3H,s), 1.80(3H,s),
1.40(9H,s), 2.17-2.28(2H,m), 2.36(2H,d,J=8.2Hz), 2.47(3H,s),
3.02(1H,d,J=5.0Hz), 3.84(3H,s), 4.00(1H,d,J=7.8Hz), 4.07-4.16(1H,m),
4.29(1H,AB type d,J=8.2Hz), 4.39(1H,AB type d,J=8.2Hz),
4.61(1H,d,J=7.8Hz), 5.00(1H,s), 5.12(1H,s), 5.22-5.36(2H,m),
5.41(1H,d,J=7.8Hz), 5.76(1H,s), 6.05(1H,d,J=5.0Hz),
6.11(1H,broad t,J=8.2Hz), 6.26(1H,d,J=3.6Hz),
6.34(1H,dd,J=3.6Hz,2.0Hz), 6.93(2H,d,J=8.8Hz), 7.38(1H,d,J=2.0Hz),
7.43-7.53(4H,m), 7.59(1H,t,J=7.9Hz), 8.02(2H,d,J=7.9Hz).
【０１２１】
工程３：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-ヒドロキシプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(4-メトキシベンジリデン) バッカチン III
上記工程２で得た化合物を原料に用い、実施例１の工程４と同様の反応操作を行うことにより、標記化合物を無色透明シロップ状の物質として得た。
【０１２２】
Rf=0.15 ( クロロホルム：アセトン＝7:1(v/v))
融点：148-151℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(3H,s), 1.42(9H,s), 1.56(3H,s), 1.76(6H,s), 2.10-2.26(3H,m),
2.36(3H,s), 2.31-2.48(1H,m), 2.99(1H,d,J=4.9Hz), 3.84(3H,s),
3.98(1H,d,J=7.4Hz), 4.06-4.17(1H,m), 4.30(1H, AB type d,J=8.3Hz),
4.38(1H, AB type d,J=8.3Hz), 4.57(1H,d,J=8.3Hz), 4.72(1H,d,J=3.9Hz),
5.11(1H,s), 5.38(2H,broad s), 5.43(1H,d,J=7.4Hz), 5.80(1H,s),
6.07(1H,d,J=4.9Hz), 6.15(1H,broad t,J=8.0Hz), 6.32(1H,d,J=3.8Hz),
6.36(1H,dd,J=3.8Hz,2.0Hz), 6.93(2H,d,J=8.8Hz), 7.40(1H,d,J=2.0Hz),
7.43-7.53(4H,m), 7.60(1H,t,J=7.3Hz), 8.11(2H,d,J=7.3Hz)
FAB mass : 918(M+).
【０１２３】
実施例３
【０１２４】
【化２４】
工程１：９β-13-Ｏ−アリルオキシカルボニル-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
実施例１の工程２で得た化合物 98.6 mgをテトラヒドロフラン 4.0 ml に溶解させ、-78℃で 1.64 規定 n−ブチルリチウム( ヘキサン溶液, 0.31 ml)を滴下し、5 分後にアリルオキシカルボニルクロリド 0.025 ml を添加した。30分後、-78 ℃で飽和塩化アンモニウム水溶液を注加し、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー( 展開溶媒；ヘキサン：酢酸エチル＝５：４(v/v))で精製し、標記化合物 52.8 mgを無色透明シロップ状の物質として得た。
【０１２６】
Rf=0.39 ( ヘキサン：酢酸エチル＝5:4(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.23(3H,s), 1.40(3H,s), 1.58(3H,s), 1.64(3H,s), 1.65(3H,s),
1.80(3H,s), 2.11-2.27(2H,m), 2.26-2.38(2H,m), 2.31(3H,s),
2.98(1H,d,J=4.8Hz), 3.90(1H,d,J=7.8Hz), 4.01-4.09(1H,m),
4.26(1H,AB type d,J=8.3Hz), 4.39(1H,AB type d,J=8.3Hz),
4.56(1H,d,J=6.8Hz), 4.63-4.76(2H,m), 5.11(1H,m), 5.28-5.44(2H,m),
5.56(1H,d,J=7.8Hz), 5.85-6.05(1H,m), 6.00(1H,d,J=4.8Hz),
7.47(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz).
【０１２７】
工程２：９β-13-Ｏ−アリルオキシカルボニル-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ−トリエチルシリルバッカチン III
上記工程１で得た化合物 52.8 mgを乾燥した塩化メチレン 2.2 ml に溶解させ、室温で 2,6−ルチジン 0.036 ml を添加した。-40 ℃に冷却し、トリエチルシリルトリフルオロメタンスルホナート 0.062 ml を滴下し、25分間撹拌した。-40 ℃で飽和重曹水を加え、クロロホルムで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー( 展開溶媒；ヘキサン：酢酸エチル＝4:1(v/v)) で精製し、標記化合物 34.1 mgを無色透明シロップ状の物質として得た。
【０１２８】
Rf=0.32 ( ヘキサン：酢酸エチル=3:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.56-0.71(6H,m), 1.15(3H,s), 1.39(3H,s), 1.47(3H,s), 1.51(3H,s),
1.58(3H,s), 1.81(3H,s), 2.05-2.15(1H,m), 2.20-2.34(2H,m),
2.30(3H,s), 2.39(1H,dd,J=7.6Hz,14.0Hz), 3.22(1H,d,J=5.8Hz),
3.95(1H,dd,J=3.4Hz,9.8HZ), 4.28(1H,AB type d,J=7.8Hz),
4.47(1H,AB type d,J=7.8Hz), 4.56(1H,broad d,J=9.3Hz),
4.68(2H,d,J=5.9Hz), 4.82(1H,t,J=7.2Hz), 5.27-5.33(1H,m),
5.34-5.41(1H,m), 5.43(1H,d,J=9.3Hz), 5.82-6.01(1H,m),
5.86(1H,d,J=7.8Hz), 5.88(1H,t,J=7.6Hz), 7.47(2H,t,J=7.8Hz),
7.58(1H,t,J=7.8Hz), 8.09(2H,d,J=7.8Hz).
【０１２９】
工程３：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ−トリエチルシリルバッカチン III
上記工程２で得た化合物 32.1 mgをテトラヒドロフラン 1.0 ml に溶解させ、室温でメタノール 0.005 ml 、テトラキストリフェニルホスフィンパラジウム 4.3 mg を添加し、窒素雰囲気下で1 時間撹拌した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー( 展開溶媒; ヘキサン：酢酸エチル＝5:3(v/v)) で精製し、標記化合物 17.1 mgを無色透明シロップ状の物質として得た。
【０１３０】
Rf=0.29 ( ヘキサン：酢酸エチル＝5:3(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.61(6H,q,J=7.8Hz), 0.96(9H,t,J=7.8Hz), 1.11(3H,s), 1.40(3H,s),
1.50(3H,s), 1.57(3H,s), 1.59(3H,s), 1.93(3H,s), 1.88-2.15(2H,m),
2.23-2.47(2H,m), 2.32(3H,s), 3.16(1H,d,J=5.3Hz), 4.17(1H,t,J=4.8Hz),
4.17-4.29(1H,m), 4.20(1H,AB type d,J=7.8Hz),
4.29(1H,AB type d,J=7.8Hz), 4.73-4.88(2H,m), 5.51(1H,d,J=7.8Hz),
5.91(1H,d,J=5.3Hz), 7.48(2H,t,J=7.3Hz), 7.59(1H,t,J=7.3Hz),
8.14(2H,d,J=7.3Hz).
【０１３１】
工程４：９β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-(tert-ブチルジメチルシリルオキシ)-3-(4−ピリジル) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ−トリエチルシリルバッカチン III
上記工程３で得た化合物を原料に用い、実施例１の工程３と同様にシス-1-(tert−ブトキシカルボニル)-3-(tert-ブチルジメチルシリルオキシ)-4-(4−ピリジル) アゼチジン-2−オンとの反応操作を行うことにより、２' 位と３' 位の相対的立体配置がスレオ（シン）型である２種のジアステレオ異性体の混合物である標記化合物を無色透明シロップ状の物質として得た。
【０１３２】
Rf=0.32 ( ヘキサン：酢酸エチル＝5:4(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.30-0.37(m), 0.60-1.02(m), 1.25-1.88(m), 2.10-2.58(m),
2.24 and 2.54(total 3H,each s),
3.10 and 3.15(total 1H,each d,J=5.4Hz and J=5.9Hz), 3.92-4.18(m),
4.21-4.60(m), 4.84 and 4.94(total 1H,each t,J=6.3Hz and J=4.8Hz),
5.21-5.68(m), 5.88 and 5.94(total 1H,each d,J=5.9Hz and J=5.4Hz),
6.18-6.30(m), 7.18-7.64(m), 8.11(2H,d,J=7.3Hz), 8.52-8.70(m).
【０１３３】
工程５：９β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程４で得られた化合物 27.1 mgをピリジン 1.35 mlに溶解させ、0 ℃でフッ化水素ピリジン 0.27 mlを滴下し、室温で6 時間撹拌した。0 ℃で冷却した水を加え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（クロロホルム：メタノール＝12:1(v/v) ）で精製し、標記化合物において２' 位と３' 位の相対的立体配置がスレオ（シン）型である２種のジアステレオ異性体のうち、低極性異性体Ａおよび高極性異性体Ｂをそれぞれ無色透明シロップ状の物質として得た。
【０１３４】
異性体Ａ
Rf=0.27 ( クロロホルム：メタノール＝12:1(v/v))
融点: 157-159 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.40(3H,s), 1.51(3H,s), 1.58(3H,s), 1.63(3H,s),
1.66(3H,s), 1.42(9H,s), 1.92(1H,broad s), 1.96-2.02(2H,m),
2.16-2.41(2H,m), 2.30(3H,s), 2.89(1H,d,J=4.4Hz), 3.77(1H,d,J=7.4Hz),
4.03-4.12(1H,m), 4.35(1H,AB type d,J=8.8Hz),
4.38(1H,AB type d,J=8.8Hz), 4.63(1H,s), 4.68(1H,d,J=8.3Hz),
5.11(1H,s), 5.30(1H,broad d,J=9.8Hz), 5.52(1H,broad d,J=7.4Hz),
5.74(1H,broad d,J=9.8Hz), 6.06(1H,d,J=4.4Hz), 6.10(1H,t,J=7.8Hz),
7.35(2H,d,J=5.9Hz), 7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.10(2H,d,J=7.8Hz), 8.59(2H,d,J=5.9Hz)
FAB mass : 851(MH+).
【０１３５】
異性体Ｂ
Rf=0.25 ( クロロホルム：メタノール＝12:1(v/v))
融点: 160-163 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.29(3H,s), 1.40(3H,s), 1.59(3H,s), 1.63(3H,s), 1.68(3H,s),
1.81(3H,s), 1.40(9H,s), 1.92(1H,broad s), 2.05-2.42(4H,m),
2.19(3H,s), 2.93(1H,d,J=4.9Hz), 3.83(1H,d,J=7.3Hz), 4.03-4.13(1H,m),
4.32(1H,AB type d,J=8.3Hz), 4.39(1H,AB type d,J=8.3Hz),
4.51(1H,broad s), 4.73(1H,d,J=7.3Hz), 5.18(1H,s like),
5.30(1H,broad d,J=8.4Hz), 5.46-5.61(2H,m), 6.06(1H,d,J=4.9Hz),
6.23(1H,m), 7.42(2H,d,J=6.8Hz), 7.46(2H,t,J=7.6Hz),
7.60(1H,t,J=7.6Hz), 8.10(2H,d,J=7.6Hz), 8.62(2H,d,J=6.8Hz)
FAB mass : 851(MH+).
【０１３６】
実施例４
【０１３７】
【化２５】
工程１：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
実施例１の工程１で得た化合物を原料に用い、2,2-ジメトキシプロパンの代わりにアクロレインジエチルアセタールを使用し、実施例１の工程２と同様の反応操作を行うことにより、標記化合物を得た。
【０１３９】
Rf=0.30 ( クロロホルム：アセトン＝5:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.17(3H,s), 1.62(3H,s), 1.65(3H,s), 1.92(3H,s), 1.82(1H,s),
1.98(1H,dd,J=16.0Hz,6.8Hz), 2.09-2.42(3H,m), 2.34(3H,s),
3.05(1H,d,J=4.4Hz), 3.89(1H,d,J=6.8Hz), 4.06-4.16(1H,m),
4.32(1H,AB type d,J=8.3Hz), 4.40(1H,AB type d,J=8.3Hz),
4.59(1H,d,J=7.8Hz), 4.82(1H,broad q,J=6.8Hz), 5.07(1H,s),
5.22(1H,d,J=6.3Hz), 5.30(1H,d,J=6.8Hz), 5.45(1H,d,J=10.3Hz),
5.56(1H,d,J=17.6Hz), 6.04(1H,d,J=4.4Hz), 5.96-6.11(1H,m),
7.48(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz), 8.13(2H,d,J=7.3Hz).
【０１４０】
工程２：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2-フリル)-2-( トリイソプロピルシリルオキシ) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
上記工程１で得た化合物を原料に用い、実施例１の工程３と同様の反応操作を行うことにより、標記化合物を得た。
【０１４１】
Rf=0.16 ( クロロホルム：アセトン＝12:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.91-1.03(21H,m), 1.30(3H,s), 1.64(3H,s), 1.68(3H,s), 1.75(3H,s),
1.40(9H,s), 1.89(1H,s), 2.21(2H,m), 2.33(2H,d,J=8.8Hz), 2.46(3H,s),
2.96(1H,d,J=4.9Hz), 3.91(1H,d,J=6.9Hz), 4.05-4.14(1H,m),
4.30(1H,AB type d,J=8.3Hz), 4.40(1H,AB type d,J=8.3Hz),
4.63(1H,d,J=8.3Hz), 5.00(1H,s), 5.12(1H,s), 5.19(1H,d,J=6.4Hz),
5.24(1H,d,J=6.9Hz), 5.22-5.34(2H,m), 5.45(1H,d,J=10.3Hz),
5.57(1H,d,J=17.5Hz), 5.94-6.15(2H,m), 6.05(1H,d,J=4.9Hz),
6.25(1H,d,J=2.9Hz), 6.34(1H,dd,J=2.9Hz,1.9Hz), 7.37(1H,d,J=1.9Hz),
7.47(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz).
【０１４２】
工程３：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-ヒドロキシプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
上記工程２で得た化合物を原料に用い、実施例１の工程４と同様の反応操作を行うことにより、標記化合物を無色透明シロップ状の物質として得た。
【０１４３】
Rf=0.05 ( クロロホルム：アセトン＝12:1(v/v))
融点: 147-150 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.28(3H,s), 1.62(3H,s), 1.69(3H,s), 1.71(3H,s), 1.41(9H,s),
2.05-2.26(3H,m), 2.29-2.44(1H,m), 2.35(3H,s), 2.93(1H,d,J=4.9Hz),
3.89(1H,d,J=6.8Hz), 4.04-4.16(1H,m), 4.32(1H,AB type d,J=8.3Hz),
4.39(1H,AB type d,J=8.3Hz), 4.71(1H,s), 5.10(1H,s),
5.22(1H,d,J=5.9Hz), 5.27(1H,d,J=6.8Hz), 5.32-5.46(2H,m),
5.46(1H,d,J=10.8Hz), 5.57(1H,d,J=17.6Hz), 5.97-6.19(2H,m),
6.08(1H,d,J=4.9Hz), 6.32(1H,d,J=1.9Hz), 6.36(1H,dd,J=3.0Hz,1.9Hz),
7.39(1H,d,J=3.0Hz), 7.48(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.10(2H,d,J=7.8Hz)
FAB mass : 838(MH+).
【０１４４】
実施例５
【０１４５】
【化２６】
工程１：９β-7−Ｏ−アリル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-( トリイソプロピルシリルオキシ) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
実施例１の工程３で得た化合物 34.4 mgをテトラヒドロフラン 1.4 ml に溶解させ、-50℃で 1規定ナトリウムヘキサメチルジシラジド( テトラヒドロフラン溶液, 0.14 ml)を滴下し、5 分後にヨウ化アリル 0.020 ml を同じ温度で加え、1.5 時間撹拌し、再び、-42℃でヨウ化アリル 0.020 ml を添加し、1.5 時間撹拌した。-40 ℃で飽和塩化アンモニウム水溶液を注加し、酢酸エチルで抽出した。飽和食塩水で洗浄して無水硫酸ナトリウムで乾燥した後、溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝5:1(v/v)) で精製し、Rf=0.12のところから７位の水酸基がエーテル化された標記化合物 2.6 mg を無色透明シロップ状の物質として得た。また、 Rf=0.27のところから４位のアセチル基がアリル化された化合物 4.2 mgを得た。
【０１４７】
Rf=0.12 ( ヘキサン：酢酸エチル＝6:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.90-1.02(m), 1.22(3H,s), 1.36(3H,s), 1.38(9H,s), 1.51(3H,s),
1.53(3H,s), 1.57(3H,s), 1.77(3H,s), 2.02-2.48(4H,m), 2.44(3H,s),
3.23(1H,d,J=5.8Hz), 3.45(1H,dd,J=2.9Hz,9.8Hz),
3.84(1H,dd,J=12.7Hz,5.4Hz), 4.17(1H,dd,J=12.7Hz,5.4Hz),
4.26(1H,AB type d,J=7.8Hz), 4.56(1H,AB type d,J=7.8Hz),
4.32(1H,d,J=8.8Hz), 4.82(1H,t,J=6.4Hz), 4.96(1H,s),
5.14(1H,dd,J=10.3Hz,1.0Hz), 5.21-5.36(2H,m), 5.42(1H,d,J=8.8Hz),
5.87(1H,d,J=5.8Hz), 5.82-5.98(1H,m), 6.14(1H,broad t,J=8.4Hz),
6.24(1H,d,J=2.9Hz), 6.34(1H,dd,J=2.9Hz,1.0Hz), 7.37(1H,d,J=1.0Hz),
7.47(2H,t,J=7.8Hz), 7.56(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
【０１４８】
工程２：９β-7−Ｏ−アリル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-ヒドロキシプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程１で得た化合物を原料に用い、実施例１の工程４と同様の反応操作を行うことにより、標記化合物を無色透明シロップ状の物質として得た。
【０１４９】
Rf=0.68 ( クロロホルム: アセトン＝12:1(v/v))
融点: 112-115 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.23(3H,s), 1.25(3H,s), 1.39(3H,s), 1.40(9H,s), 1.46-1.61(6H,m),
1.73(3H,s), 1.68-1.82(1H,m), 2.08-2.40(3H,m), 2.35(3H,s),
3.12(1H,d,J=3.9Hz), 3.44-3.56(1H,m), 3.83(1H,dd,J=13.0Hz,6.0Hz),
4.17(1H,dd,J=13.0Hz,4.8Hz), 4.23(1H,d,J=7.8Hz), 4.56(1H,d,J=8.3Hz),
4.70(1H,d,J=3.5Hz), 4.83(1H,t,J=4.9Hz), 5.12(1H,d,J=8.8Hz),
5.27(1H,d,J=16.1Hz), 5.35(1H,broad s), 5.46(1H,d,J=8.3Hz),
5.82-5.98(1H,m), 5.92(1H,d,J=3.9Hz), 6.14(1H,broad t,J=8.4Hz),
6.31(1H,d,J=2.9Hz), 6.37(1H,dd,J=2.9Hz,1.5Hz), 7.40(1H,d,J=1.5Hz),
7.47(2H,t,J=7.8Hz), 7.58(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz).
FAB Mass : 880(M+).
【０１５０】
実施例６
【０１５１】
【化２７】
工程１：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-( トリイソプロピルシリルオキシ) プロピオニル]-4,10−ジデアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-4−Ｏ-(4-ペンテノイル) バッカチン III
実施例５の工程１の操作により、Rf=0.27のところから４位のアセチル基がアリル化された標記化合物 4.2 mg を得た。
【０１５３】
Rf=0.27 ( ヘキサン：酢酸エチル＝6:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.91-1.04(m), 1.23(3H,s), 1.36(3H,s), 1.37(9H,s), 1.47(3H,s),
1.50-1.60(6H,m), 1.76(3H,s), 2.09(1H,ddd,J=5.2Hz,8.8Hz,14.4Hz),
2.15-2.31(2H,m), 2.40(1H,dd,J=8.8Hz,15.2Hz), 2.53-2.64(2H,m),
2.71(1H,q,J=7.6Hz), 2.87(1H,q,J=7.6Hz), 3.18(1H,d,J=5.4Hz),
3.92(1H,dd,J=8.8Hz,3.4Hz), 4.26(1H,AB type d,J=8.3Hz),
4.51(1H,AB type d,J=8.3Hz), 4.41(1H,broad d,J=8.3Hz),
4.76(1H,t,J=6.4Hz), 4.96(1H,s), 5.03(1H,q,J=10.8Hz),
5.14(1H,dd,J=17.1Hz,1.0Hz), 5.21-5.33(2H,m), 5.40(1H,d,J=8.3Hz),
5.81-5.97(1H,m), 5.89(1H,d,J=5.4Hz), 6.10(1H,t,J=8.8Hz),
6.25(1H,d,J=3.4Hz), 6.35(1H,dd,J=3.4Hz,2.8Hz), 7.36(1H,d,J=2.8Hz),
7.48(2H,t,J=7.3Hz), 7.57(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
【０１５４】
工程２：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-ヒドロキシプロピオニル]-4,10−ジデアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-4−Ｏ-(4-ペンテノイル) バッカチン III
上記工程１で得た化合物を原料に用い、実施例１の工程４の反応操作を行うことにより、標記化合物を得た。
【０１５５】
Rf=0.20 ( クロロホルム: アセトン＝10:1(v/v))
融点: 105-110 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.28(3H,s), 1.40(9H,s), 1.58(3H,s), 1.64(3H,s),
1.67(3H,s), 1.70(3H,s), 2.07-2.28(3H,m), 2.30-2.41(1H,m),
2.49-2.66(3H,m), 2.69-2.80(1H,m), 2.94(1H,d,J=4.4Hz),
3.66(1H,broad s), 3.84(1H,d,J=5.4Hz), 4.06(1H,m),
4.33(1H,AB type d,J=8.3Hz), 4.38(1H,AB type d,J=8.3Hz),
4.64-4.73(2H,m), 4.99-5.10(2H,m), 5.13(1H,dd,J=1.0Hz,17.0Hz),
5.31(1H,s), 5.54(1H,d,J=8.3Hz), 5.75-5.89(1H,m), 6.05(1H,d,J=4.4Hz),
6.10(1H,broad t,J=7.2Hz), 6.32(1H,d,J=3.4Hz),
6.36(1H,dd,J=3.4Hz,1.5Hz), 7.39(1H,d,J=1.5Hz), 7.48(2H,t,J=7.4Hz),
7.61(1H,t,J=7.4Hz), 8.13(2H,d,J=7.4Hz).
FAB Mass : 880(M+).
【０１５６】
実施例７
【０１５７】
【化２８】
工程１：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-(tert-ブチルジメチルシリルオキシ)-3-フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
実施例４の工程１で得た化合物を原料に用い、実施例１の工程３と同様にして (3R,4S)-1-(tert−ブトキシカルボニル)-3-(tert-ブチルジメチルシリルオキシ)-4-フェニルアゼチジン-2−オンと反応させ、標記化合物を無色透明シロップ状の物質として得た。
【０１５９】
Rf=0.35 ( クロロホルム: アセトン＝7:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.33(3H,s), -0.11(3H,s), 0.74(9H,s), 1.33(3H,s), 1.38(9H,s),
1.64(3H,s), 1.69(3H,s), 1.73(3H,s), 1.85(1H,s), 2.13-2.28(3H,m),
2.33(1H,dd,J=9.3Hz,14.6Hz), 2.53(3H,s), 2.96(1H,d,J=4.9Hz),
3.91(1H,d,J=7.3Hz), 4.04-4.14(1H,m), 4.33(1H,AB type d,J=8.3Hz),
4.40(1H,AB type d,J=8.3Hz), 4.53(1H,s), 4.59(1H,d,J=7.8Hz),
5.13(1H,s), 5.19(1H,d,J=5.9Hz), 5.23(1H,d,J=7.3Hz),
5.30(1H,broad d,J=8.8Hz), 5.45(1H,d,J=10.3Hz), 5.57(1H,d,J=17.6Hz),
5.96-6.10(1H,m), 6.04(1H,d,J=4.9Hz), 6.20(1H,t,J=8.8Hz),
7.18-7.41(5H,m), 7.48(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.13(2H,d,J=7.8Hz).
【０１６０】
工程２：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
上記工程１で得た化合物を用いて、実施例１の工程４と同様の反応操作を行うことにより、標記化合物を得た。
【０１６１】
Rf=0.30 ( クロロホルム: アセトン＝5:1(v/v))
融点:145-150℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.40(9H,s), 1.61(6H,s), 1.68(3H,s), 1.91(1H,s),
2.00-2.36(3H,m), 2.30(3H,s), 2.39(1H,dd,J=9.8Hz,15.2Hz),
2.90(1H,d,J=4.9Hz), 3.85(1H,d,J=6.8Hz), 4.06-4.15(1H,m),
4.16(1H,broad s), 4.32(1H,AB type d,J=8.8Hz),
4.38(1H,AB type d,J=8.8Hz), 4.57(1H,d,J=8.3Hz), 4.62(1H,broad s),
5.10(1H,s), 5.22(1H,d,J=6.3Hz), 5.26(1H,d,J=6.8Hz),
5.30(1H,broad d,J=9.7Hz), 5.97-6.13(2H,m), 6.07(1H,d,J=4.3Hz),
7.20-7.45(5H,m), 7.47(2H,t,J=7.4Hz), 7.60(1H,t,J=7.4Hz),
8.10(2H,d,J=7.4Hz).
FAB Mass : 848(MH+).
【０１６２】
実施例８
【０１６３】
【化２９】
工程１：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-ヒドロキシプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2,3-ジヒドロキシプロピリデン) バッカチン III
実施例４の工程３で得た化合物 35.1 mgをテトラヒドロフラン 1.1 ml と蒸留水 0.35 mlに溶解させ、室温で N−モルホリン-N−オキシド 26.8 mgおよび四酸化オスミウム 4.8 mg を添加した。21時間後、亜硫酸ナトリウム水溶液を加え、酢酸エチルで抽出した。飽和塩水で洗浄し、無水硫酸ナトリウムで乾燥後、溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：メタノール＝10:1(v/v) ）で精製し、標記化合物 14.1 mgを無色透明シロップ状の物質として得た。
【０１６５】
Rf=0.25 ( クロロホルム：メタノール＝8:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H,s), 1.29(3H,s), 1.41(9H,s), 1.63(3H,s), 1.69(3H,s),
1.70(3H,s), 2.00-2.55(m), 2.36(3H,s), 2.93(1H,d,J=4.9Hz),
3.70-4.00(m), 4.05-4.18(1H,m), 4.30(1H,AB type d,J=8.8Hz),
4.38(1H,AB type d,J=8.8Hz), 4.71(1H,s), 4.75-4.92(2H,m), 5.10(1H,s),
5.26(1H,d,J=4.9Hz), 5.35(1H,broad d,J=9.7Hz), 6.03(1H,d,J=7.3Hz),
6.08-6.16(1H,m), 6.31(1H,d,J=3.4Hz), 6.36(1H,dd,J=3.4Hz,1.5Hz),
7.39(1H,d,J=1.5Hz), 7.42-7.67(3H,m), 8.02-8.17(2H,m).
【０１６６】
工程２：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-ヒドロキシプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
上記工程１で得た化合物 14.1 mgをテトラヒドロフラン−水−メタノール（1:1:1(v/v)）の混合溶媒に溶解させ、室温でメタ過ヨウ素酸ナトリウム 19.7 mgを添加し、30分間撹拌した。0 ℃に冷却し、食塩水を加え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥後、溶媒を減圧留去し、得られた残分を真空乾燥した。これをエタノール 1.3 ml に溶解させ、室温で酢酸 0.10 ml, モルホリン 0.14 ml, ナトリウムシアノボロヒドリド 13.9 mgを添加し、1 時間撹拌した。反応液に飽和重曹水および飽和食塩水を加え、酢酸エチルで抽出し、飽和食塩水で洗浄した。無水硫酸ナトリウムにて乾燥後、溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（クロロホルム：メタノール＝12:1(v/v))で精製し、標記化合物 10.4 mgを無色透明シロップ状の物質として得た。
【０１６７】
Rf=0.56 ( クロロホルム：メタノール＝10:1(v/v))
融点; 149-152 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H,s), 1.41(9H,s), 1.60(3H,s), 1.65(3H,s), 1.69(3H,s),
1.89(1H,s), 2.08-2.26(3H,m), 2.35(3H,s), 2.31-2.43(1H,m),
2.54-2.70(4H,m), 2.74(1H,dd,J=5.4Hz,13.7Hz),
2.82(1H,dd,J=3.9Hz,13.7Hz), 2.92(1H,d,J=4.7Hz), 3.69-3.79(4H,m),
3.80(1H,d,J=6.9Hz), 3.87-3.94(1H,broad), 4.04-4.11(1H,m),
4.31(1H,AB type d,J=8.3Hz), 4.39(1H,AB type d,J=8.3Hz),
4.67(1H,d,J=8.3Hz), 4.71(1H,s), 5.02(1H,dd,J=5.4Hz,3.9Hz),
5.11(1H,s), 5.20(1H,d,J=6.9Hz), 5.30-5.42(2H,m), 6.04(1H,d,J=4.7Hz),
6.11(1H,broad t,J=8.0Hz), 6.31(1H,d,J=3.4Hz),
6.36(1H,dd,J=3.4Hz,2.0Hz), 7.39(1H,d,J=2.0Hz), 7.48(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz).
FAB Mass : 911(M+).
【０１６８】
実施例９
【０１６９】
【化３０】
工程１：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-7-Ｏ-(2,2,2-トリクロロエトキシカルボニル) バッカチン III
実施例４の工程１で得た化合物 100.4 mg をピリジン 3.0 ml に溶解させ、0 ℃で2,2,2-トリクロロエトキシカルボニルクロリド 0.025 ml を滴下した。30分後、0 ℃で冷却した水を加え、酢酸エチルで抽出し、1 規定塩酸、飽和重曹水、飽和食塩水で順に洗浄した。無水硫酸ナトリウムにて乾燥後、溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー( クロロホルム：アセトン＝6:1(v/v)）で精製し、標記化合物 116.7 mg を無色透明シロップ状の物質として得た。
【０１７１】
Rf=0.48 ( クロロホルム：アセトン＝5:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.16(3H,s), 1.60(3H,s), 1.62(3H,s), 1.96(3H,s), 1.80(1H,s),
1.91-2.00(1H,m), 2.20(1H,dt,J=16.0Hz,4.4Hz), 2.29-2.43(2H,m),
2.35(3H,s), 3.20(1H,d,J=4.9Hz), 3.97(1H,d,J=7.3Hz),
4.31(1H,AB type d,J=8.3Hz), 4.44(1H,AB type d,J=8.3Hz),
4.66(1H,AB type d,J=11.7Hz), 4.83(1H,AB type d,J=11.7Hz),
4.76-4.89(2H,m), 5.15(1H,dd,J=5.3Hz,3.4Hz), 5.19(1H,d,J=5.9Hz),
5.34(1H,d,J=7.3Hz), 5.46(1H,d,J=10.3Hz), 5.57(1H,d,J=17.5Hz),
5.98(1H,d,J=4.9Hz), 6.04(1H,ddd,J=17.5Hz,10.3Hz,5.9Hz),
7.48(2H,t,J=7.4Hz), 7.59(1H,t,J=7.4Hz), 8.13(2H,d,J=7.4Hz).
【０１７２】
工程２：９β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2,2-ジフルオロ-3-(2-フリル) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-7-Ｏ-(2,2,2-トリクロロエトキシカルボニル) バッカチン III
3-(tert-ブトキシカルボニルアミノ)-2,2-ジフルオロ-3-(2-フリル) プロピオン酸 0.2041 g をトルエン 4.0 ml に溶解させ、室温でジ-2−ピリジルカーボネート 0.1516 g を添加した。20分後、上記工程１で得た化合物 0.1167 g のトルエン 2.0 ml 懸濁液を加え、4-ジメチルアミノピリジン 39.９mgを添加し、65℃に加熱して16時間撹拌した。室温まで放冷し、反応液に水を加え酢酸エチルで抽出し、飽和食塩水で洗浄した。無水硫酸ナトリウムにて乾燥後、溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；クロロホルム：アセトン＝20:1(v/v) ）で精製し、標記化合物 75.5 mgを無色透明シロップ状の物質として得た。
【０１７３】
Rf=0.44 ( クロロホルム：アセトン＝20:1(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.28(3H,s), 1.43(9H,s), 1.47(3H,s), 1.62(3H,s), 1.64(3H,s),
1.90(1H,broad s), 2.19-2.40(6H,m), 3.13(1H,d,J=4.7Hz),
3.95-4.01(1H,m), 4.31(1H,AB type d,J=8.3Hz),
4.39(1H,AB type d,J=8.3Hz), 4.67(1H,AB type d,J=11.7Hz),
4.85(1H,AB type d,J=11.7Hz), 4.87-4.94(1H,m), 5.08-5.17(2H,m),
5.28(1H,t,J=8.3Hz), 5.38(1H,broad d,J=8.8Hz), 5.46(1H,d,J=10.2Hz),
5.56(1H,d,J=17.5Hz), 5.58-5.73(1H,m), 5.96(1H,d,J=4.7Hz),
6.04(1H,ddd,J=17.5Hz,10.2Hz,5.9Hz), 6.12-6.28(1H,m),
6.31-6.46(2H,m), 7.38-7.51(3H,m), 7.60(1H,t,J=7.4Hz),
8.06-8.14(2H,m).
【０１７４】
工程３：９β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2,2-ジフルオロ-3-(2-フリル) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
上記工程２で得た化合物 75.5 mgを酢酸−メタノール（1:1(v/v)）の混合溶媒 6.0 ml に溶解させ、室温で亜鉛粉末 0.1728 g を添加し、62℃で30分間撹拌した。固形物を濾過し、濾液を減圧濃縮した。これを酢酸エチルで希釈し、飽和重曹水と飽和食塩水で洗浄した。無水硫酸ナトリウムにて乾燥後、溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（クロロホルム：アセトン＝7:1(v/v)）で精製し、標記化合物 14.7 mgを無色透明シロップ状の物質として得た。
【０１７５】
Rf=0.30 ( クロロホルム：アセトン＝8:1(v/v)）
融点; 124-127 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(3H,s), 1.43(9H,s), 1.62(6H,s), 1.89(1H,s), 2.16-2.35(4H,m),
2.26(3H,s), 2.92(1H,d,J=4.9Hz), 3.83-3.94(1H,m), 4.04-4.10(1H,m),
4.28(1H,AB type d,J=8.3Hz), 4.40(1H,AB type d,J=8.3Hz),
4.60(1H,broad d,J=8.3Hz), 5.12(1H,s), 5.17-5.28(2H,m),
5.31-5.41(1H,m), 5.45(1H,d,J=10.7Hz), 5.56(1H,d,J=17.6Hz),
5.55-5.72(1H,m), 5.94-6.07(1H,m), 6.03(1H,d,J=4.9Hz),
6.12-6.25(1H,m), 6.35-6.46(2H,m), 7.42(1H,s), 7.48(2H,t,J=7.3Hz),
7.60(1H,t,J=7.3Hz), 8.06-8.14(2H,m).
FAB Mass : 858(M+).
【０１７６】
実施例１０
【０１７７】
【化３１】
工程１：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ-(2,2,2-トリクロロエトキシカルボニル) バッカチン III
実施例１の工程２で得た化合物を原料に用い、実施例９の工程１と同様の反応操作を行うことにより、標記化合物を無色透明シロップ状の物質として得た。
【０１７９】
Rf=0.33 ( クロロホルム：アセトン＝7:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.16(3H,s), 1.41(3H,s), 1.56(3H,s), 1.58(3H,s), 1.59(3H,s),
1.79(1H,s), 1.89-2.01(1H,m), 1.95(3H,s), 2.04-2.13(1H,m),
2.27-2.49(2H,m), 2.35(3H,s), 3.20(1H,d,J=4.9Hz), 3.96(1H,d,J=7.3Hz),
4.28(1H,AB type d,J=7.8Hz), 4.51(1H,AB type d,J=7.8Hz),
4.65(1H,AB type d,J=11.7Hz), 4.80(1H,AB type d,J=11.7Hz),
4.75-4.86(2H,m), 5.08-5.13(1H,m), 5.60(1H,d,J=7.3Hz),
5.96(1H,d,J=4.9Hz), 7.48(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz),
8.15(2H,d,J=7.3Hz).
【０１８０】
工程２：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ-(2,2,2-トリクロロエトキシカルボニル)-13−Ｏ−トリエチルシリルバッカチン III
上記工程１で得た化合物を原料に用い、実施例３の工程２と同様の反応操作を行うことにより、標記化合物を無色透明結晶として得た。
【０１８１】
Rf=0.45 ( ヘキサン：酢酸エチル＝3:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.55-0.71(6H,m), 1.01(9H,t,J=7.8Hz), 1.20(3H,s), 1.36(3H,s),
1.52(3H,s), 1.55(3H,s), 1.58(3H,s), 1.74(1H,s), 1.88(3H,s),
2.10(1H,dd,J=14.4Hz,8.8Hz), 2.16-2.42(3H,m), 2.28(3H,s),
3.19(1H,d,J=5.4Hz), 4.10(1H,d,J=8.3Hz), 4.30(1H,AB type d,J=7.8Hz),
4.47(1H,AB type d,J=7.8Hz), 4.67(1H,AB type d,J=11.7Hz),
4.81(1H,AB type d,J=11.7Hz), 4.90(1H,t,J=5.3Hz), 4.96(1H,t,J=8.8Hz),
5.04(1H,dd,J=7.9Hz,3.0Hz), 5.49(1H,d,J=8.3Hz), 5.84(1H,d,J=5.4Hz),
7.47(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz).
【０１８２】
工程３：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-13-Ｏ−トリエチルシリルバッカチン III
上記工程２で得た化合物を用い、実施例９の工程３と同様の反応操作を行うことにより、標記化合物を白色泡状の物質として得た。
【０１８３】
Rf=0.27 ( ヘキサン：酢酸エチル＝3:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.58-0.75(6H,m), 1.01(9H,t,J=7.8Hz), 1.24(3H,s), 1.40(3H,s),
1.56(3H,s), 1.62(6H,s), 1.80(1H,s), 1.86(3H,s), 2.03-2.31(4H,m),
2.27(3H,s), 2.94(1H,d,J=4.9Hz), 3.95(1H,d,J=7.9Hz), 3.99-4.07(1H,m),
4.28(1H,AB type d,J=8.3Hz), 4.38(1H,AB type d,J=8.3Hz),
4.61(1H,d,J=7.3Hz), 4.97(1H,t,J=8.8Hz), 5.10(1H,t,J=3.4Hz),
5.52(1H,d,J=7.9Hz), 5.95(1H,d,J=4.9Hz), 7.47(2H,t,J=7.8Hz),
7.59(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz).
【０１８４】
工程４：9β-7-Ｏ−アリル-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-13-Ｏ−トリエチルシリルバッカチン III
上記工程３で得た化合物 0.2400 g を乾燥したテトラヒドロフラン 7.2 ml に溶解させ、-50 ℃で 1.64 規定ブチルリチウム（ヘキサン溶液、0.315 ml）を滴下し、17分後にヨウ化アリル（0.15 ml ）のジメチルスルホキシド（1.80 ml ）溶液を添加し、0 ℃で1.5 時間撹拌した。0 ℃で飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝10:3(v/v) ）で精製し、標記化合物 0.1358 g を白色固体として得た。
【０１８５】
Rf=0.41 ( ヘキサン：酢酸エチル＝3:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.59-0.74(6H,m), 1.01(9H,t,J=7.8Hz), 1.37(3H,s), 1.43(3H,s),
1.50(3H,s), 1.57(3H,s), 1.65(1H,s), 1.87(3H,s), 2.00-2.14(2H,m),
2.21-2.47(2H,m), 2.28(3H,s), 3.26(1H,d,J=5.8Hz),
3.42(1H,dd,J=11.7Hz,3.4Hz), 3.85(1H,dd,J=12.7Hz,5.4Hz),
4.18(1H,dd,J=12.7Hz,5.4Hz), 4.29(1H,AB type d,J=7.8Hz),
4.54(1H,AB type d,J=7.8Hz), 4.40(1H,d,J=9.8Hz), 4.82(1H,t,J=8.3Hz),
4.93(1H,t,J=8.3Hz), 5.16(1H,dd,J=10.3Hz,1.5Hz),
5.32(1H,dd,J=17.1Hz,1.5Hz), 5.41(1H,d,J=9.8Hz), 5.77(1H,d,J=5.8Hz),
5.85-6.00(1H,m), 7.46(2H,t,J=7.3Hz), 7.58(1H,t,J=7.3Hz),
8.07(2H,d,J=7.3Hz).
【０１８６】
工程５：9β-7-Ｏ−アリル-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程４で得た化合物を用い、実施例１の工程４と同様の反応操作を行うことにより、標記化合物を無色透明シロップ状の物質として得た。
【０１８７】
Rf=0.05 ( ヘキサン：酢酸エチル＝2:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.12(3H,s), 1.40(3H,s), 1.54(3H,s), 1.55(3H,s), 1.58(3H,s),
1.74(1H,s), 1.94(3H,s), 1.99-2.38(4H,m), 2.3(3H,s),
3.22(1H,d,J=5.4Hz), 3.57(1H,dd,J=6.9Hz,2.5Hz),
3.83(1H,dd,J=12.4Hz,5.6Hz), 4.09-4.27(2H,m), 4.23(1H,d,J=7.7Hz),
4.60(1H,d,J=7.7Hz), 4.72-4.88(2H,m), 5.11(1H,dd,J=10.3Hz,1.4Hz),
5.26(1H,dd,J=17.0Hz,1.4Hz), 5.52(1H,d,J=7.3Hz), 5.81-5.96(2H,m),
7.46(2H,t,J=7.8Hz), 7.58(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz).
【０１８８】
工程６：９β-7−Ｏ−アリル-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-(tert-ブチルジメチルシリルオキシ)-3-フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程５で得た化合物を用い、実施例１の工程３と同様の反応操作で 1-(tert−ブトキシカルボニル)-3-(tert-ブチルジメチルシリルオキシ)-4-フェニルアゼチジン-2−オンと反応させ、標記化合物を無色透明シロップ状の物質として得た。
【０１８９】
Rf=0.17 ( ヘキサン：酢酸エチル＝2:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.32(3H,s), -0.12(3H,s), 0.74(9H,s), 1.25(3H,s), 1.36(3H,s),
1.36(9H,s), 1.51(3H,s), 1.53(3H,s), 1.57(3H,s), 1.75(3H,s),
2.06-2.12(2H,m), 2.15-2.35(1H,m), 2.42(1H,dd,J=14.7Hz,9.8Hz),
2.53(3H,s), 3.22(1H,d,J=5.9Hz), 3.46(1H,dd,J=9.8Hz,2.0Hz),
3.85(1H,dd,J=12.2Hz,5.4Hz), 4.18(1H,dd,J=12.2Hz,5.8Hz),
4.28(1H,AB type d,J=8.3Hz), 4.58(1H,AB type d,J=8.3Hz),
4.33(1H,d,J=8.8Hz), 4.50(1H,s), 4.83(1H,t,J=6.8Hz),
5.15(1H,dd,J=10.7Hz,1.4Hz), 5.22-5.36(1H,m),
5.31(1H,dd,J=17.2Hz,1.4Hz), 5.40(1H,d,J=8.8Hz), 5.41-5.54(1H,m),
5.87(1H,d,J=5.9Hz), 5.81-5.98(1H,m), 6.22(1H,t,J=8.8Hz),
7.19-7.42(5H,m), 7.47(2H,t,J=7.3Hz), 7.57(1H,t,J=7.3Hz),
8.11(2H,d,J=7.3Hz).
【０１９０】
工程７：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-(tert-ブチルジメチルシリルオキシ)-3-フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-7−Ｏ-(2,3-ジヒドロキシプロピル)-9,10−Ｏ−イソプロピリデンバッカチン III
上記工程６で得た化合物を用い、実施例８の工程１と同様の反応操作により、標記化合物を無色透明シロップ状の物質として得た。
【０１９１】
Rf=0.29 ( クロロホルム：アセトン＝4:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.32(3H,s), -0.11(3H,s), 0.74(9H,s), 1.31(3H,s), 1.37(9H,s),
1.39(3H,s), 1.52(3H,s), 1.57(3H,s), 1.60(3H,s), 1.74(3H,s),
1.94-2.42(m), 2.53(3H,s), 3.03 and 3.06(total 1H,each d,J=4.9Hz),
3.45-3.81(m), 3.88-4.02(m), 4.21-4.38(m), 4.47(d,J=7.7Hz),
4.50-4.58(m), 4.90-5.01(m), 5.23-5.36(m), 5.40-5.54(m),
5.92 and 5.94(total 1H,each d,J=4.9Hz), 5.94(d,J=4.9Hz),
7.21-7.40(5H,m), 7.48(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz),
8.13(2H,d,J=7.8Hz).
【０１９２】
工程８：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-(tert-ブチルジメチルシリルオキシ)-3-フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-7−Ｏ-(2-モルホリノエチル)-9,10−Ｏ−イソプロピリデンバッカチン III上記工程７で得た化合物を用い、実施例８の工程２と同様の反応操作により、標記化合物を無色透明シロップ状の物質として得た。
【０１９３】
Rf=0.74 ( クロロホルム：メタノール＝12:1(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.33(3H,s), -0.12(3H,s), 0.74(9H,s), 1.26(3H,s), 1.35(9H,s),
1.39(3H,s), 1.50(3H,s), 1.52(3H,s), 1.57(3H,s), 1.74(3H,s),
1.59-1.80(4H,m), 2.05-2.33(3H,m), 2.36-2.52(3H,m), 2.52(3H,s),
3.18(1H,d,J=5.4Hz), 3.35-3.49(2H,m), 3.60-3.84(5H,m),
4.19-4.33(1H,m), 4.26(1H,AB type d,J=8.3Hz),
4.55(1H,AB type d,J=8.3Hz), 4.50(1H,s), 4.83(1H,t,J=6.4Hz),
5.30(1H,broad d,J=8.0Hz), 5.86(1H,d,J=5.4Hz), 6.22(1H,t,J=8.8Hz),
7.28-7.41(5H,m), 7.48(2H,t,J=7.8Hz), 7.58(1H,t,J=7.8Hz),
8.11(2H,d,J=7.8Hz).
【０１９４】
工程９：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-7−Ｏ-(2-モルホリノエチル)-9,10−Ｏ−イソプロピリデンバッカチン III
上記工程８で得た化合物を用い、実施例１の工程４と同様の反応操作により、標記化合物を無色透明シロップ状の物質として得た。
【０１９５】
Rf=0.23 ( クロロホルム：メタノール＝15:1(v/v) ）
融点：128-133 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.23(3H,s), 1.39(9H,s), 1.41(3H,s), 1.51(3H,s), 1.58(6H,s),
1.59(3H,s), 1.50-1.86(2H,m), 1.81(1H,broad s), 1.96-2.47(4H,m),
2.30(3H,s), 2.48-2.62(4H,m), 3.03(1H,d,J=4.0Hz), 3.32-3.43(1H,m),
3.46-3.57(1H,m), 3.59-3.84(4H,m), 4.07-4.23(2H,m),
4.52(1H,d,J=7.8Hz), 4.60(1H,s), 4.83(1H,s),
5.22-5.33(1H,broad d,J=8.4Hz), 5.46(1H,d,J=7.8Hz),
5.59(1H,broad d,J=8.4Hz), 5.93(1H,d,J=4.0Hz), 6.10(1H,t,J=8.3Hz),
7.21-7.43(5H,m), 7.47(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz),
8.11(2H,d,J=7.8Hz).
【０１９６】
実施例１１
【０１９７】
【化３２】
工程１：９β-13-Ｏ-[(2R,3S)-Ｎ-(tert−ブトキシカルボニル)-Ｎ, Ｏ-(4-メトキシベンジリデン)-3-フェニルイソセリニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-プロぺニリデン)-7-Ｏ-(2,2,2-トリクロロエトキシカルボニル) バッカチン III
(2R,3S)-Ｎ-(tert−ブトキシカルボニル)-Ｎ, Ｏ-(4-メトキシベンジリデン)-3-フェニルイソセリン 70.1 mg を乾燥した塩化メチレン 2.1 ml と乾燥したトルエン 2.1 ml の混合溶媒に溶解させ、0 ℃でジシクロヘキシルカルボジイミド 34.0 mgを添加した。12分後、実施例９の工程１で得た化合物 78.1 mgを乾燥した塩化メチレン 2.5 ml に溶解させた溶液を滴下し、4-ジメチルアミノピリジン 4.2 mg を添加し、室温で2 時間撹拌した。0 ℃に冷却し、反応液を濾過し、濾過物をトルエンで洗浄した。この濾液をクロロホルムで希釈し、水および飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：アセトン＝20：１(v/v) ）で精製し、標記化合物 68.9 mgを白色ガラス状物質として得た。
【０１９９】
Rf=0.18 （クロロホルム：アセトン＝20：１(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.05(12H,s), 1.24(3H,s), 1.45(3H,br-s), 1.58(3H,s), 1.74(3H,br-s),
1.77(1H,s), 2.07(1H,d,J=14.7Hz,J=8.3Hz), 2.13-2.35(3H,m),
3.04(1H,d,J=4.9Hz), 3.81(3H,s), 3.93(1H,d,J=7.8Hz),
4.24(1H,d,J=8.3Hz), 4.35(1H,d,J=8.3Hz), 4.58(1H,d,J=4.9Hz),
4.65(1H,d,J=11.7HZ), 4.79(1H,t,J=4.9Hz), 4.83(1H,d,J=11.7Hz),
5.03(1H,dd,J=6.9Hz,J=4.0Hz), 5.10(1H,d,J=5.9Hz), 5.20(1H,d,J=7.8Hz),
5.34-5.48(1H,br), 5.45(1H,d,J=10.2Hz), 5.55(1H,d,J=17.1Hz),
5.87(1H,d,J=4.9Hz), 5.93-6.1(2H,m), 6.25-6.46(1H,br),
6.90(2H,d,J=8.8Hz), 7.32-7.52(7H,m), 7.47(2H,t,J=7.3Hz),
7.60(1H,t,J=7.3Hz), 8.05(2H,d,J=7.3Hz).
【０２００】
工程２：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−プロピリデン-7−Ｏ-(2,2,2-トリクロロエトキシカルボニル) バッカチン III
上記工程１で得た化合物 68.9 mgをエタノール 3.4 ml に溶解させ、室温で 10 ％水酸化パラジウム 8.6mgを添加し、水素雰囲気下で5 時間撹拌し、再び 10 ％水酸化パラジウム 8.6mgを添加して2 時間撹拌した。反応系を窒素で置換し、反応液を濾過した。濾過物を酢酸エチルで洗浄し、濾液の溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：アセトン＝20：１(v/v) ）で精製し、標記化合物 28.4 mgを白色ガラス状物質として得た。
【０２０１】
Rf=0.40 （クロロホルム：アセトン＝20：１(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.03(3H,t,J=7.8Hz), 1.25(3H,s), 1.40(9H,s), 1.59(3H,s), 1.61(3H,s),
1.64(3H,s), 1.74-1.93(3H,m), 2.01-2.23(2H,m), 2.30(3H,s),
2.30-2.45(2H,m), 3.04(1H,d,J=4.9Hz), 3.88(1H,d,J=7.3Hz),
4.21-4.34(2H,m), 4.43(1H,d,J=8.3Hz), 4.62(1H,br-s),
4.65(1H,d,J=12.2Hz), 4.76(1H,t,J=5.4Hz), 4.85(1H,d,J=12.2Hz),
4.90(1H,br-s), 5.14(1H,br-t,J=4.4Hz), 5.24(1H,d,J=7.3Hz),
5.31(1H,d,J=9.2Hz), 5.66(1H,d,J=9.2Hz), 6.00(1H,d,J=4.9Hz),
6.09(1H,t,J=7.8Hz), 7.20-7.46(5H,m), 7.47(2H,t,J=7.3Hz),
7.60(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
【０２０２】
工程３：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−プロピリデンバッカチン III
上記工程２で得た化合物 28.4 mgをジオキサン−メタノール−酢酸（１：１：１(v/v））の混合溶媒 2.8 ml に溶解させ、室温で亜鉛粉末 66.2 mgを添加し、5 時間撹拌した後、55℃で16時間撹拌した。反応液をそのまま濾過し、濾過物をクロロホルムで洗浄し、濾液の溶媒を減圧留去した。得られた残分を酢酸エチルで希釈し、飽和重曹水および飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：アセトン＝10：１(v/v) ）で精製し、標記化合物 10.8 mg白色ガラス状物質として得た。
【０２０３】
Rf=0.18 （クロロホルム：アセトン＝20：１(v/v) ）
融点 132-139℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.04(3H,t,J=7.9Hz), 1.26(6H,s), 1.40(9H,s), 1.60(3H,s), 1.66(3H,s),
1.73-1.91(2H,m), 1.88(1H,s), 1.98-2.14(2H,m), 2.17-2.33(1H,m),
2.30(3H,s), 2.37(1H,dd,J=15.1Hz,J=9.7Hz), 2.91(1H,d,J=4.8Hz),
3.78(1H,d,J=7.3Hz), 4.02-4.19(2H,m), 4.33(1H,d,J=8.3Hz),
4.37(1H,d,J=8.3Hz), 4.55-4.68(2H,m), 4.80(1H,t,J=5.4Hz),
5.10(1H,s like), 5.19(1H,d,J=7.3Hz), 5.29(1H,br-d,J=8.3Hz),
5.63(1H,br-d,J=8.3Hz), 6.05(1H,d,J=4.8Hz), 6.08(1H,t,J=8.8Hz),
7.20-7.45(5H,m), 7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.10(2H,d,J=7.8Hz).
FAB Mass : 850(M++1).
【０２０４】
実施例１２
【０２０５】
【化３３】
工程１：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ-(4-ニトロフェノキシカルボニル) バッカチン III
実施例１の工程２で得た化合物 70 mgを乾燥したしたテトラヒドロフラン 2 ml に溶解し -78℃に冷却した。次いで、同温度にてノルマルブチルリチウム 0.16ml （1.64 mol/ml ヘキサン溶液）を滴下した。滴下終了後、同温度にて10分間撹拌した。次いで、 同温度にてクロルギ酸 4−ニトロフェニル 29 mgを 1 ml のテトラヒドロフランに溶解した溶液を滴下した。1 時間撹拌後、反応液を徐々に０℃まで昇温させ、２時間撹拌した。反応液に飽和塩化アンモニウム溶液を加えた後、酢酸エチルで希釈し抽出した。抽出液を飽和食塩水で洗浄後、無水硫酸マグネシウムで乾燥させたのち溶媒を減圧留去した。得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒; クロロホルム：アセトン＝97:3 (v/v)) にて精製することにより標記化合物 23 mgを得た。
【０２０７】
1H-NMR(CDCl3/TMS) δ(ppm) :
1.18(3H,s), 1.43(3H,s), 1.57(3H,s), 1.59(3H,s), 1.62(3H,s),
1.63-1.80(1H,m), 1.90-2.09(2H,m), 1.96(3H,s), 2.25-2.41(1H,m),
2.36(3H,s), 3.18(1H,d,J=5Hz), 3.94(1H,d,J=7Hz), 4.18(1H,J=8Hz),
4.25(1H,8Hz), 4.78-4.89(1H,m), 4.83-4.88(1H,m), 5.13-5.17(1H,m),
5.63(1H,d,J=7Hz), 5.94(1H,d,J=5Hz), 7.31(2H,d,J=9Hz),
7.49(2H,t,J=8Hz), 7.55-7.60(1H,m), 8.12(2H,d,J=7Hz),
8.21(2H,d,J=9Hz).
【０２０８】
工程２：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ-[(4−メチルピペラジン-1−イル) カルボニル] バッカチン III
上記工程1 で得た化合物 37 mgをアセトニトリル 2 ml に溶かした溶液に N−メチルピペラジン 50 mgを室温にて滴下した。同温度にて 5時間撹拌後、溶媒を減圧留去した。得られた残分をシリカゲル薄層クロマトグラフィー( 展開溶媒; クロロホルム :メタノール = 95:5(v/v)) にて精製することにより標記化合物 9 mg を得た。
【０２０９】
1H-NMR(CDCl3/TMS) δ(ppm) :
1.14(3H,s), 1.38(3H,s), 1.52(3H,s), 1.55(3H,s), 1.56(3H,s),
1.68-1.80(1H,m), 1.95(3H,s), 2.01-2.16(2H,m), 2.27(3H,s),
2.24-2.38(5H,m), 2.34(3H,s), 3.24(1H,d,J=5Hz), 3.30-3.57(4H,m),
4.04(1H,d,J=8Hz), 4.29(1H,J=8Hz), 4.43(1H,8Hz), 4.79-4.87(1H,m),
4.84(1H,d,J=4Hz), 5.16-5.19(1H,m), 5.56(1H,d,J=8Hz),
5.92(1H,d,J=5Hz), 7.49(2H,t,J=8Hz), 7.61(1H,t,J=8Hz),
8.15(2H,d,J=7Hz).
【０２１０】
工程３：９β-13-Ｏ-[(2R,3S)-3-(tert−ブトキシカルボニルアミノ)-2-(tert-ブチルジメチルシリルオキシ)-3-フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ-[(4−メチルピペラジン-1−イル) カルボニル] バッカチン III
上記工程２で得た化合物を原料に用い、実施例１の工程３と同様に 1-(tert−ブトキシカルボニル)-3-(tert-ブチルジメチルシリルオキシ)-4-フェニルアゼチジン-2−オンと反応させて、標記化合物を白色の非晶質固体として得た。
【０２１１】
1H-NMR(CDCl3/TMS) δ(ppm) :
-0.33(3H,s), -0.12(3H,s), 0.74(9H,s), 1.25(3H,s), 1.28(3H,s),
1.33(6H,s), 1.36(3H,s), 1.53(3H,s), 1.55(9H,s), 1.63-1.80(1H,m),
1.75(3H,s), 2.00-2.20(2H,m), 2.31(3H,s), 2.20-2.45(5H,m),
2.54(3H,s), 3.21(1H,d,J=5Hz), 3.39-3.64(4H,m), 4.12(1H,d,J=9Hz),
4.32(1H,d,J=8Hz), 4.47(1H,d,J=8Hz), 4.52(1H,brs), 4.91(1H,m),
5.10(1H,m), 5.28-5.33(1H,m), 5.44(1H,d,J=9Hz), 5.42-5.49(1H,m),
5.89(1H,d,J=5Hz), 6.20-6.23(1H,m), 7.23-7.40(5H,m),
7.50(2H,t,J=8Hz), 7.60(1H,t,J=8Hz), 8.14(2H,d,J=8Hz).
【０２１２】
工程４：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ-[(4−メチルピペラジン-1−イル) カルボニル] バッカチン III上記工程３で得た化合物 13 mgを蒸留したピリジン 1 ml に溶解し、0 ℃で 0.2 ml のフッ化水素−ピリジンを加えた。滴下終了後、室温まで昇温させて1 夜間撹拌した。反応液を水で希釈後、酢酸エチルで抽出した。抽出液を飽和食塩水で洗浄後、無水硫酸マグネシウムで乾燥させたのち溶媒を減圧留去した。得られた残分をシリカゲル薄層クロマトグラフィー( 展開溶媒; クロロホルム : メタノール = 95:5(v/v)) にて精製することにより標記化合物 5 mg を得た。
【０２１３】
1H-NMR(CDCl3/TMS) δ(ppm) :
1.24(3H,s), 1.37(3H,s), 1.39(3H,s), 1.53(3H,s), 1.56(9H,s),
1.60-1.80(1H,m), 1.62(3H,s), 2.00-2.20(2H,m), 2.20-2.42(5H,m),
2.26(3H,s), 2.32(3H,s), 3.09(1H,d,J=5Hz), 3.31-3.58(4H,m),
4.03(1H,d,J=9Hz), 4.27(1H,d,J=8Hz), 4.41(1H,d,J=8Hz),
4.62(1H,broad s), 4.88(1H,m), 5.16(1H,m), 5.30(1H,m),
5.49(1H,d,J=7Hz), 5.59(1H,m), 5.95(1H,m), 6.10(1H,brt,J=8Hz),
7.23-7.40(5H,m), 7.49(2H,t,J=8Hz), 7.61(1H,t,J=7Hz),
8.13(2H,d,J=7Hz).
【０２１４】
実施例１３
【０２１５】
【化３４】
工程１：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-(tert-ブチルジメチルシリルオキシ)-3-フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ-(2-ジメチルアミノエチル) バッカチン III
実施例１０の工程７で得た化合物を原料に用い、モルホリンの代わりにジメチルアミンを使用し、実施例８の工程２と同様の操作を行うことにより、標記化合物を白色ガラス状の固体として得た。
【０２１７】
Rf=0.53 （クロロホルム：メタノール＝５：１(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.32(3H,s), -0.11(3H,s), 0.75(9H,s), 1.27(3H,s), 1.36(9H,s),
1.40(3H,s), 1.52(3H,s), 1.55(3H,s), 1.57(3H,s), 1.74(3H,s),
2.09-2.26(2H,m), 2.31-2.51(8H,m), 2.53(3H,s), 2.63-2.86(2H,m),
3.13(1H,d,J=5.3Hz), 3.46-3.63(2H,m), 3.76-3.89(1H,br),
4.12-4.25(1H,br), 4.28(1H,d,J=7.8Hz), 4.49(1H,d,J=7.8Hz),
4.52(1H,br), 4.90(1H,t,J=4.4Hz), 5.22-5.36(1H,m), 5.38-5.52(2H,m),
5.88(1H,d,J=5.3Hz), 6.21(1H,t,J=8.5Hz), 7.19-7.41(5H,m),
7.50(2H,t,J=7.4Hz), 7.59(1H,t,J=7.4Hz), 8.11(2H,d,J=7.4Hz).
【０２１８】
工程２：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ-(2-ジメチルアミノエチル) バッカチン III
上記工程１で得た化合物を原料に用い、実施例３の工程５と同様の操作を行うことにより、標記化合物を白色ガラス状固体として得た。
【０２１９】
Rf=0.32 （クロロホルム：アセトン＝20：１(v/v) ）
融点 119-121℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.22(3H,s), 1.38(9H,s), 1.41(3H,s), 1.51(3H,s), 1.58(9H,s),
1.80(1H,s), 2.04-2.37(10H,m), 2.26(3H,s), 2.52(2H,t like,J=5.9Hz),
3.04(1H,d,J=4.4Hz), 3.31-3.43(1H,m), 3.46-3.57(1H,m),
3.70-3.81(1H,m), 4.14-4.28(1H,br), 4.20(1H,d,J=7.8Hz),
4.51(1H,d,J=7.8Hz), 4.60(1H,s like), 4.84(1H,t like,J=5.0Hz),
5.27(1H,br-d,J=8.0Hz), 5.46(1H,d,J=7.6Hz), 5.59(1H,br-d,J=8.0Hz),
5.92(1H,d,J=4.4Hz), 6.10(1H,t,J=7.8Hz), 7.21-7.43(5H,m),
7.47(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz).
FAB Mass : 921(M+).
【０２２０】
実施例１４
【０２２１】
【化３５】
工程１：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-(tert-ブチルジメチルシリルオキシ)-3-フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-7−Ｏ−カルボキシメチル-9,10-Ｏ−イソプロピリデンバッカチン III
実施例１０の工程７で得た化合物 67.2 mgをテトラヒドロフラン−メタノール−水（１：１：１(v/v））の混合溶媒 3 ml に溶解させ、室温でメタ過ヨウ素酸ナトリウム 55.3 mgを添加し、1 時間撹拌した。0 ℃で冷却した水を加え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分 48.0 mgのうち 22.0 mgをジオキサン 1.65 mlおよび水 0.55 mlに溶解させ、室温でスルファミン酸 5.6 mg および亜塩素酸ナトリウム 5.3 mg を添加し、30分間撹拌した。反応液に水を加え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：メタノール＝15：１(v/v) ）で精製し、標記化合物 21.3 mgを白色固体物質として得た。
【０２２３】
Rf=0.39 （クロロホルム：メタノール＝10：１(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.32(3H,s), -0.11(3H,s), 0.74(9H,s), 1.33(3H,s), 1.37(9H,s),
1.39(3H,s), 1.58(6H,s), 1.63(3H,s), 1.74(3H,s), 1.81(1H,s),
2.02-2.40(4H,m), 2.54(3H,s), 3.04(1H,d,J=4.9Hz), 3.68(1H,br),
3.80-4.03(2H,m), 4.33(1H,d,J=7.8Hz), 4.54(1H,d,J=7.8Hz),
4.44-4.62(1H,m), 5.05(1H,br), 5.30(1H,d,J=8.3Hz),
5.45(1H,d,J=8.3Hz), 5.52(1H,d,J=7.3Hz), 5.94(1H,d,J=4.9Hz),
6.20(1H,t,J=8.8Hz), 7.18-7.42(5H,m), 7.49(2H,t,J=7.9Hz),
7.60(1H,t,J=7.9Hz), 8.12(2H,d,J=7.9Hz).
【０２２４】
工程２：９β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-7−Ｏ−カルボキシメチル-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程１で得た化合物を原料に用い、実施例３の工程５と同様の操作を行うことにより標記化合物を白色ガラス状の固体として得た。
【０２２５】
Rf=0.40 （クロロホルム：メタノール＝10：１(v/v) ）
融点 157-160℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H,s), 1.40(3H,s), 1.41(9H,s), 1.53(3H,s), 1.56(3H,s),
1.58(3H,s), 1.63(3H,s), 1.86(1H,s), 1.92-2.13(2H,m),
2.26-2.44(2H,m), 2.32(3H,s), 2.95(1H,d,J=4.4Hz), 3.71(1H,br-s),
3.78(1H,br-d,J=6.0Hz), 3.90(1H,d,J=6.6Hz), 3.97-4.11(1H,br),
4.29(1H,d,J=8.3Hz), 4.30-4.44(1H,m), 4.54(1H,d,J=8.3Hz),
4.62(1H,br-s), 5.04(1H,br-s), 5.27(1H,d,J=8.3Hz),
5.53(1H,d,J=6.8Hz), 5.60(1H,d,J=8.3Hz), 5.97(1H,d,J=4.4Hz),
6.10(1H,t,J=7.8Hz), 7.22-7.43(5H,m), 7.47(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
FAB Mass : 908(M++1).
【０２２６】
実施例１５
【０２２７】
【化３６】
工程１：９β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-メチル-2−トリエチルシリルオキシ-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ−トリエチルシリルバッカチン III
実施例３の工程３で得た化合物を原料として用い、実施例１の工程３と同様にしてシス-1-(tert−ブトキシカルボニル)-3-メチル-4−フェニル-3-(トリエチルシリルオキシ) アゼチジン-2−オンと反応させて、標記化合物を無色のガラス状固体として得た。
【０２２９】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.50-0.72(12H,m), 0.87(9H,t,J=8Hz), 0.97(9H,t,J=8Hz), 1.29(9H,s),
1.34(3H,s), 1.38(3H,s), 1.41(3H,s), 1.51(3H,s), 1.57(3H,s),
1.59(3H,s), 1.73(3H,s), 2.00-2.18(3H,m), 2.34(1H,dd,J=15Hz,10Hz),
2.64(3H,s), 3.07(1H,d,J=5.5Hz), 4.00(1H,dd,J=8Hz,3.5Hz),
4.24(1H,d,J=8Hz), 4.34(1H,br-d,J=8Hz), 4.56(1H,d,J=8Hz),
4.86(1H,t,J=5.5Hz), 4.98(1H,d,J=10Hz), 5.42(1H,d,J=9Hz),
5.52(1H,d,J=10Hz), 5.91(1H,d,J=5.5Hz), 6.28(1H,t,J=9Hz),
7.27-7.36(10H,m), 7.48(2H,t,J=7.5Hz), 7.58(1H,t,J=7.5Hz),
8.15(2H,d,J=7.5Hz).
【０２３０】
工程２：９β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2−メチル-3−フェニルプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程１で得た化合物を実施例１の工程４と同様に反応させ、標記化合物を無色ガラス状の固体として得た。
【０２３１】
融点 180-182℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.32(3H,s), 1.35(9H,s), 1.40(6H,s), 1.58(3H,s), 1.60(3H,s),
1.64(3H,s), 1.68(3H,s), 2.08-2.31(4H,m), 2.51(3H,s),
2.91(1H,d,J=4.5Hz), 3.80(1H,d,J=7Hz), 3.99(1H,s), 4.08(1H,m),
4.36(1H,AB type d,J=9Hz), 4.39(1H,AB typed,J=9Hz), 4.70(1H,d,J=8Hz),
5.01(1H,d,J=10Hz), 5.11(1H,br-s), 5.50(1H,d,J=7Hz),
5.67(1H,d,J=10Hz), 6.05(1H,d,J=4.5Hz), 6.22(1H,t,J=8Hz),
7.28-7.41(10H,m), 7.48(2H,t,J=7.5Hz), 7.60(1H,t,J=7.5Hz),
8.13(1H,d,J=7.5).
FAB Mass : 865(M++1).
【０２３２】
実施例１６
【０２３３】
【化３７】
工程１：９β-13-Ｏ-[(2R,3S)-Ｎ-(tert−ブトキシカルボニル)-Ｎ, Ｏ-(4-メトキシベンジリデン)-3-フェニルイソセリニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(プロペニリデン) バッカチン III
実施例１１の工程１で得た化合物を原料に用い、 実施例１１の工程３と同様の反応操作を行うことにより、 標記化合物をガラス状の固体として得た。
【０２３５】
Rf=0.35 （クロロホルム：アセトン＝15：１(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.04(12H,s), 1.27(3H,s), 1.43(3H,br s), 1.64(3H,s), 1.72(3H,br s),
1.83(1H,s), 1.97-2.27(4H,m), 2.82(1H,d,J=5.3Hz), 3.81(3H,s),
3.85(1H,d,J=7.4Hz), 3.96-4.07(1H,m), 4.22(1H,d,J=8.3Hz),
4.32(1H,d,J=8.3Hz), 4.48(1H,d,J=7.4Hz), 4.58(1H,d,J=5.4Hz),
4.98(1H,s like), 5.17(2H,d,J=5.9Hz), 5.32-5.49(1H,br),
5.44(1H,d,J=10.8Hz), 5.55(1H,d,J=17.8Hz), 5.90-6.12(3H,m),
6.22-6.47(1H,br), 6.90(2H,d,J=8.8Hz), 7.31-7.50(9H,m),
7.59(1H,t,J=7.4Hz), 8.03(2H,d,J=7.4Hz).
【０２３６】
工程２：９β-13-Ｏ-[(2R,3S)-Ｎ-(tert−ブトキシカルボニル)-Ｎ, Ｏ-(4-メトキシベンジリデン)-3-フェニルイソセリニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ-(2-Ｎ−モルホリノエチリデン) バッカチン III
上記工程１で得た化合物 149.4 mg をテトラヒドロフラン 4.48 mlと水 1.49 mlの混合溶媒に溶解させ、室温で N−メチルモルホリン-N−オキシド 87.2 mgとオスミウムテトラオキシド 7.8 mg を添加し、 遮光下で 8時間撹拌した後、オスミウムテトラオキシド 3.6 mg を添加し、16時間撹拌した。飽和亜硫酸ナトリウム水溶液を加え、室温で 10 分間撹拌してから酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥後、溶媒を減圧留去した。得られた残分をテトラヒドロフラン、水、およびメタノール（1:1:1 (v/v) ）の混合溶媒 4.1 ml に溶解させ、室温でメタ過ヨウ素酸ナトリウム 118.6 mg を添加し、40分間撹拌した。0 ℃に冷却し、冷水を加え、さらに飽和食塩水を加えて酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分 126.2 mg のうち 65.2 mgをエタノール 4 ml に溶解させ、室温で酢酸 0.04 ml、モルホリン 0.059 ml 、10% 水酸化パラジウム 14.0 mgを添加し、水素雰囲気下で 5時間撹拌した。反応系内を窒素置換し、内容物を濾過し、その濾液を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：アセトン＝５：１(v/v) ）で精製し、標記化合物 18.4 mgを無色透明シロップとして得た。
【０２３７】
Rf=0.17 （クロロホルム：アセトン＝５：１(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.04(3H,s), 1.27(3H,s), 1.41(3H,br s), 1.56(3H,s), 1.61(3H,s),
1.71(3H,br s), 1.99-2.25(4H,m), 2.52-2.86(7H,m), 3.66-3.86(5H,m),
3.81(3H,s), 4.00(1H,br s), 4.21(1H,d,J=8.3Hz), 4.32(1H,d,J=8.3Hz),
4.57(1H,d,J=4.9Hz), 4.92-5.03(2H,m), 5.10(1H,d,J=7.4Hz),
5.40(1H,br), 5.93(1H,d,J=4.9Hz), 6.05(1H,br), 6.20-6.48(1H,br),
6.90(2H,d,J=8.8Hz), 7.31-7.51(9H,m), 7.60(1H,t,J=7.3Hz),
8.03(2H,d,J=7.3Hz).
【０２３８】
工程３：９β-13-Ｏ-[(2R,3S)-３-(tert−ブトキシカルボニルアミノ)-2-ヒドロキシ-3−フェニルプロピオニル-10-デアセチル-9−ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
上記工程２で得た化合物を原料に用い、実施例１１の工程２と同様の反応操作を行うことにより、標記化合物を無色透明シロップ状の物質として得た。
【０２３９】
Rf=0.20 （クロロホルム：アセトン＝15：１(v/v) ）
融点：129-132 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(6H,s), 1.40(9H,s), 1.59(3H,s), 1.65(3H,s), 1.88(1H,s),
1.96-2.46(4H,m), 2.30(3H,s), 2.50-2.70(4H,m),
2.74(1H,dd,J=18.4Hz,J=4.4Hz), 2.83(1H,dd,J=18.4Hz,J=4.4Hz),
2.90(1H,d,J=4.9Hz), 3.63-3.86(5H,m), 4.02-4.18(2H,m),
4.32(1H,d,J=8.3Hz), 4.38(1H,d,J=8.3Hz), 4.63(1H,s like),
4.66(1H,d,J=8.3Hz), 5.02(1H,t,J=3.9Hz), 5.10(1H,s like),
5.19(1H,d like,J=6.9Hz), 5.29(1H,d,J=10.0Hz), 5.61(1H,d,J=10.0Hz),
6.00-6.13(2H,m), 7.19-7.53(7H,m), 7.59(1H,t,J=7.3Hz),
8.11(2H,d,J=7.3Hz).
FAB Mass：921 (M+).
【０２４０】
同様にして以下の化合物を合成した。なお、表中のＰｈはフェニル基を意味する。
【０２４１】
【化３８】
【表１】
【表２】
【表３】
【表４】
【表５】
実施例１７
9 β-9,10-Ｏ-(2-ベンジルアミノエチリデン)-13- Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロバッカチンIII
【０２４８】
融点；125-128 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.40(9H,s), 1.56(6H,s), 1.63(3H,s), 1.80-2.45(5H,m),
2.30(3H,s), 2.89(1H,d,J=4.9Hz), 2.99(2H,d,J=4.9Hz),
3.80(1H,d,J=6.8Hz), 3.88(2H,s), 4.08(1H,br s), 4.31(1H,d,J=8.3Hz),
4.37(1H,d,J=8.3Hz), 4.62(1H,s), 5.00(1H,t,J=4.9Hz), 5.10(1H,s),
5.21(1H,d,J=6.8Hz), 5.29(1H,d,J=8.8Hz), 5.64(1H,d,J=8.8Hz),
6.00-6.15(2H,m), 7.22-7.56(7H,m), 7.60(1H,t,J=7.3Hz),
8.10(2H,d,J=7.3Hz).
FAB mass：941(MH+)
【０２４９】
実施例１８
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-[2-(4- チオモルホリニル) エチリデン] バッカチンIII
【０２５０】
融点；149-152 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.40(9H,s), 1.56(3H,s), 1.58(3H,s), 1.64(3H,s),
1.88(1H,s), 2.00-2.45(3H,m), 2.30(3H,s), 2.62-2.96(11H,m),
3.77(1H,d,J=7.3Hz), 4.03-4.21(2H,m), 4.31(1H,d,J=8.8Hz),
4.38(1H,d,J=8.8Hz), 4.57-4.70(2H,m), 4.99(1H,t,J=4.9Hz), 5.10(1H,s),
5.18(1H,d,J=6.9Hz), 5.29(1H,d,J=8.3Hz), 5.62(1H,d,J=8.3Hz),
6.00-6.17(2H,m), 7.23-7.46(7H,m), 7.60(1H,t,J=7.4Hz),
8.10(2H,d,J=7.4Hz).
FAB mass：937(MH+)
【０２５１】
実施例１９
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(2-ジメチルアミノエチリデン) バッカチンIII
【０２５２】
融点；148-149 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.38(9H,s), 1.55(3H,s), 1.58(3H,s), 1.64(3H,s),
1.87(1H,s), 1.9-2.43(4H,m), 2.28(3H,s), 2.35(6H,s),
2.67(1H,dd,J=13.2Hz,J=7.8Hz), 2.75(1H,dd,J=13.2Hz,J=3.4Hz),
2.88(1H,d,J=4.9Hz), 3.76(1H,d,J=7.3Hz), 4.07(1H,br s),
4.30(1H,d,J=8.8Hz), 4.36(1H,d,J=8.8Hz), 4.60(2H,br s),
4.98(1H,dd,J=5.4Hz,J=3.4Hz), 5.08(1H,s), 5.18(1H,d,J=7.3Hz),
5.27(1H,d,J=9.3Hz), 5.61(1H,d,J=9.3Hz), 6.00-6.18(2H,m),
7.20-7.55(7H,m), 7.60(1H,t,J=7.8Hz), 8.09(2H,d,J=7.8Hz).
FAB mass：879(MH+)
【０２５３】
実施例２０
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０２５４】
融点；125-128 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.02(3H,t,J=7.3Hz), 1.28(3H,s), 1.41(9H,s), 1.62(3H,s), 1.69(3H,s),
1.71(3H,s), 1.75-1.94(2H,m), 1.81(1H,s), 2.10-2.28(3H,m),
2.29-2.52(3H,m), 2.54-2.68(1H,m), 2.94(1H,d,J=4.9Hz),
3.79-3.95(1H,br), 3.89(1H,d,J=6.8Hz), 4.04-4.16(1H,m),
4.32(1H,d,J=8.7Hz), 4.39(1H,d,J=8.7Hz), 4.59(1H,d,J=8.3Hz),
4.70(1H,s), 5.05(1H,s), 5.21(1H,d,J=5.8Hz), 5.27(1H,d,J=6.8Hz),
5.27-5.40(2H,m), 5.46(1H,d,J=10.2Hz), 5.57(1H,d,J=17.5Hz),
6.04(1H,ddd,J=17.5Hz,J=10.2Hz,J=5.8Hz), 6.08(1H,d,J=4.9Hz),
6.05-6.15(1H,m), 6.33(1H,d,J=2.9Hz), 6.36(1H,dd,J=2.9Hz,J=1.9Hz),
7.39(1H,d,J=1.9Hz), 7.47(2H,t,J=7.8Hz), 7.61(1H,t,J=7.8Hz),
8.12(2H,d,J=7.8Hz).
FAB mass：866(MH+)
【０２５５】
実施例２１
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０２５６】
融点；127-130 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.99(3H,t,J=7.3Hz), 1.26(3H,s), 1.29(3H,s), 1.40(3H,s), 1.61(3H,s),
1.67(3H,s), 1.73-1.88(2H,m), 1.92(1H,br s), 2.00-2.46(3H,m),
2.91(1H,d,J=4.9Hz), 3.86(1H,d,J=6.8Hz), 4.09(1H,br s),
4.32(1H,d,J=8.8Hz), 4.38(1H,d,J=8.8Hz), 4.50-4.68(2H,m),
5.04(1H,s like), 5.21(1H,d,J=6.4Hz), 5.21-5.32(2H,m),
5.45(1H,d,J=10.7Hz), 5.56(1H,d,J=17.1Hz), 5.62(1H,d,J=9.8Hz),
5.97-6.12(3H,m), 7.22-7.52(7H,m), 7.60(1H,t,J=7.8Hz),
8.11(2H,d,J=7.8Hz).
FAB mass：876(MH+)
【０２５７】
実施例２２
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０２５８】
融点；123-125 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.01(3H,t,J=7.3Hz), 1.27(3H,s), 1.40(9H,s), 1.61(3H,s), 1.65(3H,s),
1.69(3H,s), 1.77-1.92(2H,m), 1.88(1H,s), 2.08-2.26(2H,m),
2.31-2.60(7H,m), 2.74(1H,dd,J=18.0Hz,J=4.4Hz),
2.83(1H,dd,J=18.0Hz,J=4.0Hz), 2.93(1H,d,J=4.9Hz),
3.73(4H,t,J=4.9Hz), 3.82(1H,d,J=6.9Hz), 4.05-4.12(1H,m),
4.31(1H,d,J=8.3Hz), 4.39(1H,d,J=8.3Hz), 4.64-4.73(2H,m),
5.02(1H,t,J=4.0Hz), 5.06(1H,s like), 5.20(1H,d,J=6.9Hz), 5.33(2H,s),
6.04(1H,d,J=4.9Hz), 6.08(1H,br t,J=8.0Hz), 6.33(1H,d,J=3.5Hz),
6.36(1H,dd,J=3.5Hz,J=1.9Hz), 7.39(1H,d,J=1.9Hz), 7.48(2H,t,J=7.8Hz),
7.61(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz). FAB mass：939(MH+)
【０２５９】
実施例２３
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０２６０】
融点；130-132 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.99(3H,t,J=7.3Hz), 1.26(3H,s), 1.40(9H,s), 1.60(3H,s), 1.64(3H,s),
1.72-1.79(2H,m), 1.80(1H,s), 2.01-2.26(3H,m), 2.30-2.43(2H,m),
2.49-2.70(5H,m), 2.75(1H,dd,J=13.2Hz,J=4.9Hz),
2.83(1H,dd,J=13.2Hz,J=3.9Hz), 2.89(1H,d,J=4.4Hz), 3.74(4H,t,J=4.4Hz),
3.78(1H,d,J=7.4Hz), 4.01-4.12(2H,m), 4.32(1H,d,J=8.7Hz),
4.38(1H,d,J=8.7Hz), 4.62(1H,br s), 4.66(1H,d,J=8.3Hz),
4.99-5.09(2H,m), 5.19(1H,d,J=6.8Hz), 5.27(1H,d,J=9.3Hz),
5.60(1H,d,J=9.3Hz), 5.60(1H,d,J=9.3Hz), 5.98-6.10(2H,m),
7.20-7.52(7H,m), 7.61(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
FAB mass：949(MH+)
【０２６１】
実施例２４
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-4- Ｏ- プロパノイル-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０２６２】
融点；135-137 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS)δ(ppm)
1.29(3H,s), 1.34(3H,t,J=7.8Hz), 1.40(9H,s), 1.63(3H,s), 1.69(3H,s),
1.71(3H,s), 1.90(1H,s), 2.10-2.26(3H,m), 2.31-2.44(1H,m),
2.51-2.73(2H,m), 2.94(1H,d,J=4.9Hz), 3.91(1H,d,J=7.4Hz),
4.09(1H,br), 4.32(1H,d,J=8.8Hz), 4.40(1H,d,J=8.8Hz),
4.55(1H,br d,J=7.4Hz), 4.69(1H,s), 5.03(1H,s like),
5.21(1H,d,J=5.9Hz), 5.26(1H,d,J=7.4Hz), 5.29-5.39(2H,m),
5.45(1H,d,J=10.7Hz), 5.57(1H,d,J=17.6Hz), 5.97-6.06(3H,m),
6.33(1H,d,J=2.9Hz), 6.36(1H,dd,J=2.9Hz,J=2.0Hz), 7.39(1H,d,J=2.0Hz),
7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz), 8.13(2H,d,J=7.8Hz).
FAB mass：852(MH+)
【０２６３】
実施例２５
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン)-4-Ｏ- プロピオニルバッカチンIII
【０２６４】
融点；145-148 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.28(3H,s), 1.32(3H,t,J=7.6Hz), 1.40(9H,s), 1.61(3H,s), 1.66(3H,s),
1.70(3H,s), 1.89(1H,s), 2.09-2.26(3H,m), 2.51-2.70(6H,m),
2.75(1H,dd,J=12.4Hz,J=5.6Hz), 2.82(1H,dd,J=12.4Hz,J=4.0Hz),
2.93(1H,d,J=4.9Hz), 3.74(4H,t,J=4.4Hz), 3.83(1H,d,J=7.4Hz),
4.04-4.12(1H,m), 4.32(1H,d,J=8.3Hz), 4.41(1H,d,J=8.3Hz),
4.66(1H,d,J=8.3Hz), 4.66(1H,s), 4.99-5.08(2H,m), 5.20(1H,d,J=7.4Hz),
5.32(2H,s like), 6.05(1H,d,J=4.9Hz), 6.10(1H,br t,J=7.8Hz),
6.33(1H,d,J=3.4Hz), 6.36(1H,dd,J=3.4Hz,J=2.0Hz), 7.39(1H,d,J=2.0Hz),
7.48(2H,t,J=7.8Hz), 7.61(1H,t,J=7.8Hz), 8.13(2H,d,J=7.8Hz).
FAB mass：925(MH+)
【０２６５】
実施例２６
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-4-Ｏ- プロピオニルバッカチンIII
【０２６６】
融点；190-192 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H,s), 1.30(3H,t,J=7.8Hz), 1.40(9H,s), 1.59(6H,br s),
1.61(3H,s), 1.68(3H,s), 1.90(1H,s), 2.02-2.24(3H,m),
2.29-2.70(4H,m), 2.91(1H,d,J=4.4Hz), 3.87(1H,d,J=6.9Hz),
3.99-4.16(2H,m), 4.32(1H,d,J=8.3Hz), 4.40(1H,d,J=8.3Hz),
4.55(1H,d,J=8.3Hz), 4.61(1H,br s), 5.03(1H,s like), 5.19-5.32(1H,m),
5.21(1H,d,J=6.4Hz), 5.25(1H,d,J=6.9Hz), 5.45(1H,d,J=10.7Hz),
5.50-5.62(1H,m), 5.56(1H,d,J=17.1Hz), 5.99-6.13(3H,m),
7.12-7.50(7H,m), 7.60(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
FAB mass：862(MH+)
【０２６７】
実施例２７
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン)-4-Ｏ- プロピオニルバッカチンIII
【０２６８】
融点；137-139 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.27(3H,s), 1.29(3H,t,J=7.3Hz), 1.39(9H,s), 1.58(3H,s),
1.65(3H,s), 1.88(1H,s), 2.02-2.26(3H,m),
2.36(1H,dd,J=14.0Hz,J=10.0Hz), 2.42-2.71(4H,m),
2.75(1H,dd,J=14.0Hz,J=4.8Hz), 2.83(1H,dd,J=14.0Hz,J=3.8Hz),
2.90(1H,d,J=4.4Hz), 3.74(1H,t,J=4.4Hz), 3.79(1H,d,J=6.8Hz),
3.92-4.13(2H,br), 4.32(1H,d,J=8.8Hz), 4.40(1H,d,J=8.8Hz),
4.56-4.67(2H,m), 5.03(1H,s like), 5.19(1H,d,J=6.8Hz),
5.22(1H,br d,J=9.2Hz), 5.55(1H,d,J=9.2Hz), 5.98-6.12(2H,m),
7.11-7.50(7H,m), 7.61(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
FAB mass：935(MH+)
【０２６９】
実施例２８
9 β-13-Ｏ-[(3S)-(tert- ブトキシカルボニルアミノ)-2,2-ジフルオロ-3-(2-フリル) プロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０２７０】
融点；176-178 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(s), 1.44(9H,s), 1.62(s), 1.69(s), 2.32(s), 2.93(1H,d,J=5Hz),
3.89(1H,d,J=7Hz), 4.08(1H,m), 4.28(1H,d,J=8.5Hz),
4.40(1H,d,J=8.5Hz), 4.61(1H,d,J=8.5Hz), 5.13(1H,br),
5.20(1H,d,J=6Hz), 5.23(1H,d,J=7Hz), 5.38(1H,d,J=12Hz),
5.45(1H,d,J=11Hz), 5.56(1H,d,J=17Hz), 5.67(1H,m), 6.03(2H,m),
6.21(1H,t,J=9Hz), 6.39(1H,dd,J=3Hz,2Hz), 6.44(1H,d,J=3Hz),
7.43(1H,d,J=2Hz), 7.48(2H,t,J=7.5Hz), 7.61(1H,t,J=7.5Hz),
8.11(2H,d,J=7.5Hz).
FAB mass：858(M+)
【０２７１】
実施例２９
9 β-13-Ｏ-[(3S)-(tert- ブトキシカルボニルアミノ)-2,2-ジフルオロ-3-(2-フリル) プロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０２７２】
融点；142-144 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(s), 1.44(9H,s), 1.61(s), 1.66(s), 2.19(2H,m), 2.28(2H,m),
2.32(3H,s), 2.62(4H,m), 2.74(1H,dd,J=13.5Hz,5Hz),
2.81(1H,dd,J=13.5Hz,5Hz), 2.91(1H,d,J=5Hz), 3.73(4H,t,J=4.5Hz),
3.81(1H,d,J=7.5Hz), 4.07(1H,br), 4.28(1H,d,J=8.5Hz),
4.41(1H,d,J=8.5Hz), 4.72(1H,d,J=8.5Hz), 5.01(1H,t,J=4.5Hz),
5.14(1H,br), 5.16(1H,d,J=7.5Hz), 5.38(1H,d,J=9Hz), 5.67(1H,m),
6.01(1H,d,J=5Hz), 6.20(1H,t,J=9Hz), 6.39(1H,dd,J=3Hz,2Hz),
6.43(1H,d,J=3Hz), 7.43(1H,d,J=2Hz), 7.49(2H,t,J=7.5Hz),
7.61(1H,t,J=7.5Hz), 8.11(2H,d,J=7.5Hz).
FAB mass：931(M+)
【０２７３】
実施例３０
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-7- Ｏ- メチル-9,10-Ｏ-(2-プロペニリデン) バッカチン III
【０２７４】
融点：137-140 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.20(3H,s), 1.40(9H,br s), 1.57(3H,s), 1.59(3H,s), 1.65(3H,s),
1.86(1H,s), 1.95-2.50(4H,m), 2.27(3H,s), 3.07(1H,d,J=4.9Hz),
3.33-3.42(1H,s), 3.38(3H,s), 4.29(1H,d,J=8.1Hz), 4.32-4.40(1H,br),
4.36(1H,d,J=8.1Hz), 4.46(1H,d,J=7.8Hz), 4.62(1H,br s),
4.89(1H,br d,J=5.4Hz), 5.17(1H,d,J=5.9Hz), 5.25-5.38(1H,m),
5.34(1H,d,J=8.3Hz), 5.48(1H,d,J=10.3Hz), 5.59(1H,d,J=17.6Hz),
5.66(1H,br d,J=9.3Hz), 5.96(1H,d,J=4.9Hz), 6.08(1H,br t,J=7.8Hz),
6.17(1H,ddd,J=5.9,10.3,17.6Hz), 7.26-7.44(5H,m), 7.46(2H,t,J=7.3Hz),
7.59(1H,t,J=7.3Hz), 8.09(2H,d,J=7.3Hz)
FAB mass : 862(MH+)
【０２７５】
実施例３１
9 β-13-Ｏ-[(2R,3S)-(3-tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-5- メチル-4- ヘキセノイル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
【０２７６】
融点；122-127 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm):
1.25(3H,s), 1.40(9H,s), 1.62(3H,s), 1.69(3H,s), 1.75(6H,s),
1.77(3H,s), 2.04-2.38(4H,m), 2.11(3H,s), 2.63(1H,s),
2.96(1H,d,J=7.5Hz), 4.11(1H,m), 4.29(1H,br),
4.36(2H,AB type q,J=8.5Hz), 4.58(1H,d,J=8.2Hz),
4.83(1H,dt,J=9.1Hz,J=2.3Hz), 4.96(1H,br), 5.12(1H,s),
5.22(1H,d,J=6.1Hz), 5.27(1H,d,J=7.9Hz), 5.28(1H,d,J=6.1Hz),
5.45(1H,d,J=10.5Hz), 5.57(1H,d,J=17.1Hz), 5.94-6.12(3H,m),
7.46(2H,t,J=7.8Hz), 7.50(1H,t,J=7.3Hz), 8.04(2H,d,J=6.8Hz).
FAB mass：826(MH+).
【０２７７】
実施例３２
9 β-9,10-Ｏ-[(2E)-4- ベンジルオキシ-2- ブテニリデン]-13- Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロバッカチンIII
【０２７８】
融点；112-115 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.40(9H,s), 1.59(3H,br s), 1.62(3H,s), 1.68(3H,s),
1.90(1H,s), 2.00-2.35(3H,m), 2.29(3H,s),
2.37(1H,dd,J=15.2Hz,J=9.8Hz), 2.90(1H,d,J=4.4Hz),
3.85(1H,d,J=6.9Hz), 4.10(2H,d,J=4.4Hz), 4.14(1H,br),
4.32(1H,d,J=8.3Hz), 4.37(1H,d,J=8.3Hz), 4.56(2H,s), 4.62(1H,br),
5.09(1H,s like), 5.21-5.36(3H,m), 5.64(1H,br d,J=9.8Hz),
5.95(1H,dd,J=15.6Hz,J=5.8Hz), 6.04-6.16(3H,m), 7.25-7.45(10H,m),
7.47(2H,t,J=7.8Hz), 7.60(1H,t J=7.8Hz), 8.10(2H,d,J=7.8Hz).
FAB mass：968(MH+)
【０２７９】
実施例３３
9 β-9,10-Ｏ-(4-ベンジルオキシブチリデン)-13- Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロバッカチンIII
【０２８０】
融点；102-105 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(6H,s), 1.40(9H,s), 1.60(3H,s), 1.64(3H,s), 1.74-1.97(5H,m),
2.01-2.43(4H,m), 2.30(3H,s), 2.90(1H,d,J=4.4Hz), 3.54(2H,t,J=6.3Hz),
3.77(1H,d,J=6.8Hz), 4.05-4.18(2H,m), 4.33(1H,d,J=8.3Hz),
4.37(1H,d,J=8.3Hz), 4.53(2H,s), 4.59-4.70(2H,m), 4.88(1H,t,J=5.4Hz),
5.10(1H,s like), 5.18(1H,d,J=6.8Hz), 5.30(1H,br d,J=9.5Hz),
5.64(1H,br d,J=9.5Hz), 6.02-6.14(2H,m), 7.22-7.43(10H,m),
7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
FAB mass：970(MH+)
【０２８１】
実施例３４
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(4-モルホリノブチリデン) バッカチンIII
【０２８２】
融点；128-131 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.40(9H,s), 1.53-1.74(2H,m), 1.60(3H,s), 1.65(6H,s),
1.81-1.93(3H,m), 2.03-2.56(9H,m), 2.30(3H,s), 2.90(1H,d,J=4.4Hz),
3.74(4H,m), 3.78(1H,d,J=6.9Hz), 4.05-4.12(1H,br),
4.32(1H,d,J=8.8Hz), 4.37(1H,d,J=8.8Hz), 4.59-4.68(2H,m),
4.87(1H,t,J=5.3Hz), 5.10(1H,s like), 5.18(1H,d,J=6.9Hz),
5.28(1H,br d,J=9.2Hz), 5.63(1H,br d,J=9.2Hz), 6.05(1H,d,J=4.4Hz),
6.08(1H,t,J=8.3Hz), 7.23-7.43(5H,m), 7.47(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
FAB mass：949(MH+)
【０２８３】
実施例３５
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(4-モルホリノブチリデン) バッカチンIII
【０２８４】
融点；127-130 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H,s), 1.41(9H,s), 1.54-1.95(m), 1.61(3H,s), 1.65(3H,s),
1.70(3H,s), 2.05-2.26(3H,m), 2.35(3H,s), 2.30-2.57(6H,m),
2.93(1H,d,J=5.3Hz), 3.74(4H,t,J=4.4Hz), 3.81(1H,d,J=7.4Hz),
4.07(1H,br), 4.32(1H,d,J=8.3Hz), 4.39(1H,d,J=8.3Hz), 4.65(1H,br),
4.71(1H,s), 4.87(1H,t,J=5.4Hz), 5.10(1H,s like), 5.20(1H,d,J=7.4Hz),
5.32-5.43(2H,m), 6.05(1H,d,J=5.3Hz), 6.10(1H,t,J=6.8Hz),
6.318(1H,d,J=2.9Hz), 6.36(1H,dd,J=2.9Hz,J=1.9Hz),
7.39(1H,d,J=1.9Hz), 7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.11(2H,d,J=7.8H).
FAB mass：939(MH+)
【０２８５】
実施例３６
9 β-9,10-Ｏ-(2-ベンジルアミノエチリデン) −4-Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-9- ジヒドロバッカチンIII
【０２８６】
融点；111-115 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.01(3H,t,J=7.3Hz), 1.27(3H,s), 1.40(9H,s), 1.58(3H,s), 1.63(3H,s),
1.70(3H,s), 1.74-2.70(12H,m), 2.93(1H,d,J=4.4Hz),
2.98(1H,d,J=4.9Hz), 3.85(1H,d,J=7.8Hz), 3.89(2H,s), 4.07(1H,s like),
4.31(1H,d,J=8.3Hz), 4.38(1H,d,J=8.3Hz), 4.69(1H,d,J=1.9Hz),
5.01(1H,t,J=5.4Hz), 5.05(1H,s like), 5.22(1H,d,J=7.8Hz),
5.31(1H,br d,J=9.8Hz), 5.37(1H,br d,J=9.8Hz), 6.02(1H,d,J=4.4Hz),
6.08(1H,br t,J=7.8Hz), 6.32(1H,d,J=3.4Hz),
6.36(1H,dd,J=3.4Hz,J=1.9Hz), 7.20-8.41(6H,m), 7.47(2H,t,J=7.3Hz),
7.60(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
FAB mass：959(MH+)
【０２８７】
実施例３７
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-ジメチルアミノエチリデン) バッカチンIII
【０２８８】
融点；125-128 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.01(3H,t,J=6.8Hz), 1.28(3H,s), 1.40(9H,s), 1.55-1.93(4H,m),
1.61(3H,s), 1.67(3H,s), 1.70(3H,s), 2.10-2.26(3H,m), 2.38(6H,s),
2.30-2.70(3H,m), 2.71(1H,dd,J=12.8Hz,J=6.0Hz),
2.80(1H,dd,J=12.8Hz,J=3.6Hz), 2.93(1H,d,J=4.9Hz),
3.82(1H,d,J=7.3Hz), 4.08(1H,br), 4.32(1H,d,J=8.3Hz),
4.39(1H,d,J=8.3Hz), 4.70(1H,s), 5.01(1H,t like,J=3.9Hz),
5.05(1H,s like), 5.21(1H,d,J=7.3Hz), 5.33(2H,br s),
6.05(1H,d,J=4.9Hz), 6.08(1H,br t,J=8.0Hz), 6.33(1H,d,J=3.4Hz),
6.36(1H,dd,J=3.4Hz,J=1.9Hz), 7.39(1H,d,J=1.9Hz), 7.47(2H,t,J=7.3Hz),
7.61(1H,d,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
FAB mass：897(MH+)
【０２８９】
実施例３８
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(3-ブテニリデン) バッカチンIII
【０２９０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.40(9H,br), 1.43(3H,s), 1.62(3H,s), 1.66(3H,s),
1.89(1H,s), 2.01-2.44(4H,m), 2.30(3H,s), 2.58(2H,t,J=6.3Hz),
2.91(1H,d,J=4.4Hz), 3.80(1H,d,J=7.3Hz), 4.10(1H,br),
4.33(1H,d,J=8.8Hz), 4.38(1H,d,J=8.8Hz), 4.58-4.71(2H,m),
4.89(1H,t,J=5.3Hz), 5.08-5.35(5H,m), 5.63(1H,br d,J=10.0Hz),
5.81-5.93(1H,m), 6.03-6.13(2H,m), 7.20-7.53(7H,m),
7.60(1H,t,J=7.3Hz), 8.11(2H,d,J=7.3Hz).
【０２９１】
実施例３９
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０２９２】
融点；108-109 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm):
1.03(3H,t,J=6.8Hz), 1.24(3H,s), 1.40(3H,s), 1.42(9H,s),
1.58(3H,s), 1.62(3H,s), 1.63(3H,s), 1.66(3H,s),
1.84(2H,q,J=6.8Hz), 2.10-2.37(5H,m), 2.54(2H,m),
2.90(1H,d,J=4.4Hz), 3.85(1H,d,J=6.8Hz), 4.09(1H,br),
4.37(2H,s like), 4.62(1H,s), 4.70(1H,d,J=8.3Hz), 5.06(1H,s),
5.29(1H,d,J=8.8Hz), 5.51(1H,d,J=6.8Hz), 5.52(1H,d,J=8.8Hz),
6.07(2H,br), 7.37(2H,d,J=5.4Hz), 7.47(1H,t,J=7.8Hz),
7.61(1H,t,J=7.8Hz), 8.12(2H,d,J=7.3Hz), 8.60(2H,d,5.9Hz).
FAB mass：879(M+).
【０２９３】
実施例４０
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-[2-( Ｎ- チアゾリジノ) エチリデン] バッカチンIII
【０２９４】
融点；114-117 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.40(9H,s), 1.57(3H,s), 1.62(3H,br), 1.65(3H,s),
1.90(1H,s), 2.02-2.45(4H,m), 2.32(3H,s), 2.75-3.24(7H,m),
3.80(1H,d,J=7.3Hz), 4.31(1H,d,J=8.3Hz), 4.37(1H,d,J=8.3Hz),
4.60-4.70(2H,m), 5.05(1H,t,J=4.3Hz), 5.10(1H,s), 5.23(1H,d,J=6.8Hz),
5.29(1H,d,J=9.0Hz), 5.62(1H,d,J=9.0Hz), 6.00-6.14(2H,m),
7.24-7.46(5H,m), 7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.10(2H,d,J=7.8Hz).
FAB mass：923(MH+)
【０２９５】
実施例４１
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-[2-(4- ピリジルメチルアミノ) エチリデン] バッカチンIII
【０２９６】
融点；138-141 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.40(9H,s), 1.58(3H,s), 1.63(6H,s), 1.90(1H,s),
2.01-2.43(4H,m), 2.30(3H,s), 2.89(1H,d,J=4.9Hz), 2.99(1H,d,J=4.9Hz),
3.82(1H,d,J=7.3Hz), 3.91(1H,s), 4.08(1H,br), 4.31(1H,d,J=8.8Hz),
4.38(1h,d,J=8.8Hz), 4.58-4.74(2H,m), 5.00(1H,t,J=4.9Hz), 5.10(1H,s),
5.23(1H,d,J=7.3Hz), 5.28(1H,d,J=9.7Hz), 5.61(1H,d,J=9.7Hz),
6.03(1H,d,J=4.9Hz), 6.10(1H,t,J=7.9Hz), 7.21-7.51(9H,m),
7.61(1H,t,J=7.4Hz), 8.10(2H,d,J=7.4Hz), 8.56(2H,d,J=5.9Hz).
FAB mass：942(MH+)
【０２９７】
実施例４２
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-[2-(2- モルホリノエチルアミノ) エチリデン] バッカチンIII
【０２９８】
融点；124-127 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.40(9H,s), 1.57(3H,s), 1.60(3H,s), 1.65(3H,s),
2.02-2.60(12H,m), 2.30(3H,s), 2.75-2.87(2H,m), 2.90(2H,d,J=4.9Hz),
2.99(1H,d,J=4.9Hz), 3.72(4H,t,J=4.4Hz), 3.81(1H,d,J=7.3Hz),
4.08(1H,s), 4.32(1H,d,J=8.3Hz), 4.37(1H,d,J=8.3Hz), 4.62(1H,s),
4.98(1H,t,J=4.9Hz), 5.10(1H,s), 5.22(1H,d,J=7.3Hz),
5.29(1H,br d,J=9.3Hz), 5.62(1H,br d,J=9.3Hz), 6.04(1H,d,J=4.9Hz),
6.09(1H,t,J=7.3Hz), 7.18-7.52(7H,m), 7.60(1H,t,J=7.4Hz),
8.10(2H,d,J=7.4Hz).
FAB mass：964(MH+)
【０２９９】
実施例４３
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-9,10- Ｏ-[2-( シクロプロピルアミノ) エチリデン]-10- アセチル-9- ジヒドロバッカチンIII
【０３００】
融点；139-142 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.35-0.54(4H,m), 1.26(3H,s), 1.40(9H,s), 1.57(3H,s), 1.61(3H,s),
1.68(3H,s), 1.89(1H,br), 2.02-2.44(5H,m), 2.30(3H,s),
2.90(1H,d,J=4.9Hz), 3.05(2H,d,J=5.3Hz), 3.80(1H,d,J=7.4Hz),
4.10(1H,s), 4.32(1H,d,J=8.3Hz), 4.38(1H,d,J=8.3Hz), 4.62(1H,s),
4.96(1H,t,J=5.3Hz), 5.10(1H,s), 5.21(1H,d,J=7.4Hz),
5.29(1H,br d,J=8.8Hz), 5.62(1H,br d,J=8.8Hz), 6.00-6.12(2H,m),
7.19-7.52(5H,m), 7.60(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
FAB mass：891(MH+)
【０３０１】
実施例４４
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9,10-Ｏ-[2-( ジエチルアミノ) エチリデン]-9-ジヒドロバッカチンIII
【０３０２】
融点；132-135 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.08(6H,t,J=7.3Hz), 1.25(3H,s), 1.40(9H,s), 1.60(3H,s), 1.62(3H,s),
1.67(3H,s), 1.88(1H,s), 1.99-2.43(4H,m), 2.29(3H,s),
2.60-2.73(4H,m), 2.80-2.93(2H,m), 2.89(1H,d,J=4.9Hz),
3.77(1H,d,J=6.8Hz), 4.10(1H,br), 4.32(1H,d,J=8.8Hz),
4.37(1H,d,J=8.8Hz), 4.58-4.69(2H,m), 4.97(1H,br), 5.10(1H,s),
5.20(1H,d,J=6.8Hz), 5.29(1H,d,J=8.8Hz), 5.62(1H,d,J=8.8Hz),
6.01-6.12(2H,m), 7.24-7.52(7H,m), 7.60(1H,t,J=7.3Hz),
8.10(2H,d,J=7.3Hz).
FAB mass：907(MH+)
【０３０３】
実施例４５
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-[2-(2- ヒドロキシエチルアミノ) エチリデン]バッカチンIII
【０３０４】
融点；149-151 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.40(9H,s), 1.57(3H,s), 1.60(3H,s), 1.64(3H,s),
1.89-2.47(m), 2.30(3H,s), 2.83-2.96(3H,m), 3.00(2H,d,J=4.9Hz),
3.67(2H,t,J=4.9Hz), 3.81(1H,d,J=7.3Hz), 4.08(1H,s),
4.31(1H,d,J=8.8Hz), 4.37(1H,d,J=8.8Hz), 4.62(1H,s),
4.97(1H,t,J=4.9Hz), 5.10(1H,s), 5.22(1H,d,J=7.3Hz),
5.28(1H,d,J=9.8Hz), 5.64(1H,d,J=9.8Hz), 6.04(1H,d,J=4.9Hz),
7.21-7.51(7H,m), 7.60(1H,t,J=7.3Hz), 8.10(2H,d,J=7.3Hz).
FAB mass：895(MH+)
【０３０５】
実施例４６
9 β-9,10-Ｏ-[2-(N- アジリジノ) エチリデン]-13- Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロバッカチンIII
【０３０６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.35(3H,s), 1.42(9H,s), 1.53(3H,s), 1.68(3H,s), 1.78(3H,s),
1.70-2.00(2H,m), 2.12-2.48(6H,m), 2.42(3H,s), 2.48-2.58(1H,m),
2.64-2.73(1H,m), 2.96(1H,d,J=4.5Hz), 3.86(1H,d,J=7.0Hz),
4.03-4.11(1H,m), 4.31(1H,d,J=8.3Hz), 4.41(1H,d,J=8.3Hz),
4.65(1H,d,J=8.5Hz), 5.03-5.32(4H,m), 5.40-5.55(2H,m),
6.01(1H,d,J=4.5Hz), 6.14-6.25(2H,m), 7.20-7.45(5H,m),
7.49(2H,t,J=7.5Hz), 7.60(1H,t,J=7.5Hz), 8.14(2H,d,J=7.5Hz).
FAB mass：859(MH+-H2O)
【０３０７】
実施例４７
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(イソプロピリデン) バッカチンIII
【０３０８】
融点：170-174 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(s), 1.37(9H,s), 1.40(s), 1.43(s), 1.58(s), 1.63(s), 1.68(s),
2.05(1H,m), 2.09(1H,m), 2.21(1H,m), 2.25(1H,m), 2.47(3H,s),
2.90(1H,d,J=4Hz), 3.77(1H,d,J=7Hz), 4.08(1H,br), 4.32(1H,br),
4.38(2H,s), 4.69(1H,d,J=8.5Hz), 5.00(1H,d,J=10Hz), 5.11(1H,br),
5.48(1H,d,J=7Hz), 5.78(1H,d,J=10Hz), 6.05(1H,d,J=4Hz), 6.23(1H,t),
7.36(2H,s-d), 7.48(2H,t,J=7.5Hz), 7.61(1H,t,J=7.5Hz),
8.12(2H,d,J=7.5Hz), 8.59(2H,s-d).
FAB mass：865(M+)
【０３０９】
実施例４８
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-イソプロピリデン-4- Ｏ- プロピオニルバッカチン III
【０３１０】
融点；140-147 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm):
1.25(3H,s), 1.33(3H,t,J=7.8Hz), 1.41(9H,s), 1.42(3H,s),
1.53(3H,s), 1.63(3H,s), 1.66(6H,s), 2.07-2.36(4H,m),
2.40-2.57(2H,m), 2.91(1H,d,J=4.9Hz), 3.80(1H,d,J=7.3Hz),
4.08(1H,br), 4.38(2H,AB type q,J=15.6Hz), 4.62(1H,s),
4.72(1H,d,J=7.9Hz), 5.04(1H,s), 5.28(1H,d,J=8.5Hz),
5.52(1H,d,J=7.3Hz), 5.70(1H,d,J=8.5Hz), 6.07(2H,br),
7.36(2H,s), 7.47(2H,t,J=7.8Hz), 7.61(1H,t,J=7.3Hz),
8.13(2H,d,J=7.3Hz), 8.60(2H,br).
FAB mass：865(M+).
【０３１１】
実施例４９
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３１２】
融点；225-228 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.04-1.16(2H,m), 1.27(3H,s), 1.41(9H,s), 1.60(3H,s),
1.60-1.75(2H,m), 1.68(3H,s), 1.74(3H,s), 1.92(1H,s),
2.03-2.32(3H,m), 2.41(1H,dd,J=14.0Hz,J=9.6Hz), 2.92(1H.d.J=4.4Hz),
3.88(1H,d,J=7.3Hz), 3.96-4.14(2H,m), 4.27(1H,d,J=8.8Hz),
4.33(1H,d,J=8.8Hz), 4.56(1H,d,J=7.8Hz), 4.71(1H,s like),
5.05(1H,s like), 5.22(1H,d,J=5.8Hz), 5.28(1H,d,J=7.3Hz),
5.37(2H,s like), 5.45(1H,d,J=10.3Hz), 5.56(1H,d,J=17.1Hz),
5.97-6.15(3H,m), 6.27-6.40(2H,m), 7.36(1H,s like),
7.48(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz), 8.05(2H,d,J=7.8Hz).
FAB mass：864(MH+)
【０３１３】
実施例５０
9 β-9,10-Ｏ-(2-アミノエチリデン)-13- Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-9- ジヒドロバッカチンIII
【０３１４】
融点；155-158 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.40(9H,s), 1.58(3H,s), 1.60(3H,s), 1.65(3H,s),
2.00-2.44(4H,m), 2.30(3H,s), 2.90(1H,d,J=4.9Hz), 3.02(2H,d,J=4.4Hz),
3.82(1H,d,J=7.4Hz), 4.09(1H,s like), 4.32(1H,d,J=8.3Hz),
4.37(1H,d,J=8.3Hz), 4.62(1H,s like), 4.84(1H,t,J=4.9Hz), 5.10(1H,s),
5.23(1H,d,J=7.4Hz), 5.28(1H,d,J=9.2Hz), 5.62(1H,d,J=9.2Hz),
6.04(1H,d,J=4.9Hz), 6.08(1H,t,J=8.3Hz), 7.20-7.56(7H,m),
7.47(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
FAB mass：851(MH+)
【０３１５】
実施例５１
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０３１６】
融点；147-148 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.01-1.19(2H,m), 1.27(3H,s), 1.41(9H,s), 1.58(3H,s), 1.65(3H,s),
1.72(3H,s), 1.92(1H,s), 2.04-2.32(3H,m),
2.40(1H,dd,J=15.1Hz,J=9.2Hz), 2.52-2.70(4H,m),
2.74(1H,dd,J=13.1Hz,J=4.8Hz), 2.90(1H,d,J=4.9Hz),
3.73(4H,t like,J=4.9Hz), 3.81(1H,d,J=6.8Hz), 4.06(1H,br),
4.26(1H,d,J=8.8Hz), 4.33(1H,d,J=8.8Hz), 4.66(1H,d,J=8.3Hz),
4.71(1H,s), 4.89-5.09(2H,m), 5.21(1H,d,J=7.4Hz), 5.37(2H,m),
6.01-6.10(2H,m), 6.29-6.39(2H,m), 7.36(1H,s like),
7.48(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz), 8.05(2H,d,J=7.8Hz).
FAB mass：937(MH+)
【０３１７】
実施例５２
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３１８】
融点；218-220 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.00-1.10(2H,m), 1.20-1.45(2H,m), 1.25(3H,s), 1.40(3H,s),
1.50-1.80(2H,m), 1.58(3H,s), 1.95(1H,s), 2.07-2.24(3H,m),
2.41(1H,dd,J=15.1Hz,J=9.8Hz), 2.88(1H,d,J=3.9Hz),
3.86(1H,d,J=6.9Hz), 4.08(1H,br), 4.26(1H,d,J=8.7Hz),
4.31(1H,d,J=8.7Hz), 4.53(1H,br d,J=7.9Hz), 5.04(1H,s),
5.21(1H,d,J=6.3Hz), 5.25-5.33(2H,m), 5.44(1H,d,J=10.7Hz),
5.56(11H,d,J=17.0Hz), 5.609(1H,d,J=8.8Hz), 5.96-6.12(3H,m),
7.24-7.51(7H,m), 7.60(1H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz),
8.03(2H,d,J=7.3Hz).
FAB mass：874(MH+)
【０３１９】
実施例５３
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０３２０】
融点；146-147 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.96-1.02(2H,m), 1.24(3H,s), 1.18-1.40(2H,m), 1.40(9H,s),
1.57(6H,s), 1.64(3H,s), 1.90-2.15(4H,m), 2.30-2.98(8H,m),
3.61-3.83(5H,m), 4.06(1H,br), 4.26(1H,d,J=8.3Hz),
4.31(1H,d,J=8.3Hz), 4.50-4.74(2H,m), 4.92-5.03(2H,m),
5.20(1H,d,J=6.4Hz), 5.27(1H,d,J=9.3Hz), 5.68(1H,d,J=9.3Hz),
5.89-6.15(2H,m), 7.17-7.52(7H,m), 7.60(1H,t,J=7.3Hz),
8.03(2H,d,J=7.3Hz).
FAB mass：947(MH+)
【０３２１】
実施例５４
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル］-4- Ｏ- ブタノイル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンハッカチンIII
【０３２２】
融点；160-163 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm):
1.11(3H,t,J=7.5Hz), 1.29(s), 1.37(9H,s), 1.40(s), 1.42(s), 1.58(s),
1.64(s), 1.67(s), 1.92(1H,m), 2.07(2H,m), 2.24(2H,m), 2.56(1H,m),
2.71(1H,m), 2.92(1H,s-d), 3.77(1H,d,J=7Hz), 4.08(1H,br),
4.30(1H,br), 4.38(2H,s), 4.71(1H,d,J=8Hz), 5.00(1H,d,J=10Hz),
5.06(1H,br), 5.48(1H,d,J=7Hz), 5.80(1H,d,J=10Hz), 6.06(1H,s-d),
6.20(1H,t-br), 7.37(2H,d,J=5Hz), 7.48(2H,t,J=7.5Hz),
7.61(1H,t,J=7.5Hz), 8.14(2H,d,J=7.5Hz), 8.59(2H,d,J=5Hz).
FAB mass：893(M+)
【０３２３】
実施例５５
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３２４】
融点；128-134 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm):
1.23(3H,s), 1.26(4H,s), 1.41(3H,s), 1.42(3H,s), 1.48(9H,s),
1.53(3H,s), 1.60(3H,s), 1.66(3H,s), 1.92-2.37(5H,m),
2.88(1H,d,J=5.3Hz), 3.76(1H,d,J=7.3Hz), 4.06(1H,m),
4.30(2H,s), 4.60(1H,br), 4.68(1H,d,J=8.3Hz), 5.06(1H,s),
5.27(1H,d,J=8.0Hz), 5.54(1H,d,J=7.3Hz), 5.89(1H,d,J=8.0Hz),
6.01(1H,t,J=7.3Hz), 6.08(1H,d,J=5.3Hz), 7.37(2H,br),
7.48(2H,t,J=7.8Hz), 7.61(1H,t,J=7.3Hz), 8.03(2H,d,J=7.3Hz),
8.59(2H,br).
FAB mass：877(MH+).
【０３２５】
実施例５６
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシ-2- メチルプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３２６】
融点；230-233 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.20-1.80(4H,m), 1.31(3H,s), 1.37(9H,s), 1.45(3H,s), 1.60(3H,s),
1.69(3H,s), 1.89-2.02(2H,m), 2.92(1H,d,J=3.9Hz), 3.86(1H,d,J=7.3Hz),
4.05-4.13(1H,m), 4.22(1H,br s), 4.29(1H,d,J=8.3Hz),
4.33(1H,d,J=8.3Hz), 4.61(1H,d,J=7.9Hz), 5.07(1H,s like),
5.16-5.29(3H,m), 5.44(1H,d,J=10.8Hz), 5.50(1H,d,J=9.7Hz),
5.56(1H,d,J=17.1Hz), 5.98-6.10(1H,m), 6.08(1H,d,J=3.9Hz),
6.20(1H,t,J=8.0Hz), 6.30(1H,d,J=3.5Hz), 6.35(1H,m), 7.36(1H,s like),
7.49(2H,t,J=7.4Hz), 7.61(1H,t,J=7.4Hz), 8.06(2H,d,J=7.4Hz).
FAB mass：878(MH+)
【０３２７】
実施例５７
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシ-2- メチルプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０３２８】
融点；140-143 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.10-1.82(4H,m), 1.31(3H,s), 1.37(9H,s), 1.58(3H,s), 1.66(6H,s),
1.67(3H,s), 1.90-2.03(1H,m), 1.92(1H,s), 2.04-2.36(4H,m),
2.50-2.70(4H,m), 2.74(1H,dd,J=13.6Hz,J=5.3Hz),
2.82(1H,dd,J=13.6Hz,J=3.4Hz), 2.90(1H,d,J=3.9Hz),
3.73(4H,t,J=4.8Hz), 3.78(1H,d,J=7.3Hz), 4.02-4.10(1H,m),
4.18(1H,br), 4.28(1H,d,J=8.8Hz), 4.34(1H,d,J=8.8Hz),
4.69(1H,d,J=8.3Hz), 5.02(1H,t,J=4.9Hz), 5.07(1H,s), 5.15-5.26(2H,m),
5.48(1H,d,J=9.8Hz), 6.06(1H,d,J=3.9Hz), 6.19(1H,t,J=8.3Hz),
6.30(1H,d,J=3.0Hz), 6.35(1H,dd,J=3.0Hz,J=2.9Hz), 7.36(1H,d,J=2.9Hz),
7.49(2H,t,J=7.8Hz), 7.61(1H,t,J=7.8Hz), 8.06(2H,d,J=7.8Hz).
FAB mass：951(MH+)
【０３２９】
実施例５８
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３３０】
融点；156-157 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.04-1.16(2H,m), 1.20-1.80(2H,m), 1.23(3H,s), 1.41(9H,s),
1.63(6H,s), 1.67(3H,s), 1.95-2.28(4H,m), 2.36-2.47(1H,m),
2.87(1H,d,J=4.4Hz), 3.85(1H,d,J=7.2Hz), 4.08(1H.br),
4.27(1H,d,J=8.8Hz), 4.30(1H,d,J=8.8Hz), 4.47-4.65(2H,m),
5.05(1H,s like), 5.21(1H,d,J=5.8Hz), 5.23-5.34(2H,m),
5.45(1H,d,J=10.3Hz), 5.56(1H,d,J=17.2Hz), 5.79(1H,d,J=9.8Hz),
6.00-6.12(3H,m), 7.35(2H,d,J=5.8Hz), 7.47(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.02(2H,d,J=7.8Hz), 8.57(2H,d,J=5.8Hz).
FAB mass：875(MH+)
【０３３１】
実施例５９
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-(4-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３３２】
融点：162.5-167.5 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.23(3H,s), 1.43(9H,s), 1.51(3H,s), 1.55(3H,s), 1.57(3H,s),
1.61(3H,s), 1.71(3H,s), 1.60-2.10(5H,m), 1.97(1H,s), 2.28(3H,s),
2.34(1H,dd,J=10.2,J=15.1Hz), 2.91(1H,d,J=4.9Hz), 4.12(1H,d,J=7.1Hz),
4.27(1H,d,J=8.3Hz), 4.32(1H,d,J=8.3Hz), 4.63(1H,br s),
4.82(1H,br s), 4.93(1H,br s), 5.30(1H,d,J=9.1Hz),
5.56(1H,d,J=7.1Hz), 5.81(1H,d,J=9.1Hz), 6.00(1H,d,J=4.9Hz),
6.09(1H,br t,J=7.8Hz), 7.36(2H,d,J=5.9Hz), 7.47(2H,t,J=7.3Hz),
7.60(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz), 8.59(2H,d,J=5.9Hz)
【０３３３】
実施例６０
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３３４】
融点；152-158 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm):
1.16(4H,m), 1.28(3H,s), 1.39(9H,s), 1.40(3H,s), 1.42(3H,s),
1.58(3H,s), 1.60(3H,s), 1.67(3H,s), 1.83-2.36(5H,m),
2.89(1H,d,J=3.9Hz), 3.74(1H,d,J=7.3Hz), 4.07(1H,m),
4.32(2H,s), 4.70(1H,d,J=8.3Hz), 5.00(1H,d,J=10.3Hz),
5.07(1H,s), 5.49(1H,d,J=6.8Hz), 5.87(1H,d,J=9.8Hz),
6.08(1H,d,J=4.4Hz), 6.20(1H,m), 7.38(2H,d,J=5.9Hz),
7.49(2H,t,J=7.8Hz), 7.62(1H,t,J=7.3Hz), 8.04(2H,d,J=7.3Hz),
8.57(2H,d,J=5.4Hz).
FAB mass：891(MH+).
【０３３５】
実施例６１
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３３６】
融点；130-133 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.00-1.10(2H,m), 1.20-1.40(2H,m), 1.24(3H,s), 1.41(9H,s),
1.45(3H,s), 1.62(3H,s), 1.62-2.10(6H,m), 2.01(3H,s),
2.38(1H,dd,J=14.7Hz,J=8.8Hz), 2.89(1H,d,J=4.4Hz),
4.14(1H,d,J=7.0Hz), 4.18(1H,d,J=8.8Hz), 4.27(1H,d,J=8.8Hz),
4.60(1H,br s). 4.65(1H,br s), 4.87(1H,s), 5.23(1H,d,J=5.9Hz),
5.20-5.20(1H,m), 5.29(1H,d,J=5.9Hz), 5.46(1H,d,J=10.7Hz),
5.57(1H,d,J=17.6Hz), 5.74(1H,d,J=9.8Hz), 5.95-6.08(3H,m),
7.29(1H,d,J=7.3Hz), 7.34(2H,t,J=7.3Hz), 7.42(2H,d,J=7.3Hz),
7.47(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz), 8.04(2H,d,J=7.3Hz).
FAB mass：858(MH+)
【０３３７】
実施例６２
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３３８】
融点；132-135 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.03-1.13(2H,m), 1.25(3H,s), 1.30-1.50(2H,m), 1.41(9H,s),
1.46(3H,s), 1.63(3H,s), 1.71-1.95(5H,m), 1.78(3H,br s),
2.01-2.21(2H,m), 2.40(1H,dd,J=15.1Hz,J=9.8Hz), 2.91(1H,d,J=4.9Hz),
4.14-4.22(2H,m), 4.29(1H,d,J=8.3Hz), 4.33(1H,br s), 4.71(1H,s),
4.87(1H,s), 5.24(1H,d,J=6.3Hz), 5.31(1H,d,J=6.8Hz),
5.37(1H,br d,J=9.8Hz), 5.44(1H,br d,J=9.8Hz), 5.46(1H,d,J=10.8Hz),
5.57(1H,d,J=17.1Hz), 5.93-6.10(3H,m), 6.31(1H,d,J=2.9Hz),
6.34(1H,dd,J=2.9Hz,J=1.9Hz), 7.36(1H,s like), 7.48(2H,t,J=7.4Hz),
7.61(1H,t,J=7.43Hz), 8.06(2H,d,J=7.4Hz).FAB mass：848(MH+)
【０３３９】
実施例６３
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０３４０】
融点；118-121 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.00-1.09(2H,m), 1.24(3H,s), 1.20-1.40(2H,m), 1.40(9H,s),
1.43(3H,s), 1.50-2.21(6H,m), 1.55-1.62(6H,m),
2.39(1H,dd,J=14.5Hz,J=10.2Hz), 2.53-2.82(5H,m), 2.86(1H,d,J=3.9Hz),
3.74(4H,t,J=4.9Hz), 4.08(1H,d,J=7.3Hz), 4.18(1H,d,J=8.8Hz),
4.26(1H,d,J=8.8Hz), 4.61(1H,br), 4.86(1H,br s),
5.04(1H,dd,J=4.4Hz,J=3.4Hz), 5.23(1H,d,J=7.3Hz), 5.29(1H,d,J=8.3Hz),
5.73(1H,d,J=8.3Hz), 5.95-6.06(2H,m), 7.21-7.30(1H,),
7.41(2H,d,J=7.3Hz), 7.47(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz),
8.04(2H,d,J=7.3Hz).
FAB mass：931(MH+)
【０３４１】
実施例６４
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０３４２】
融点；129-132 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.02-1.12(2H,m), 1.26(3H,s), 1.34-1.49(2H,m), 1.41(9H,s),
1.60(6H,s), 1.70-2.21(6H,m), 1.76(3H,s),
2.39(1H,dd,J=15.2Hz,J=9.7Hz), 2.53-2.82(6H,m), 2.90(1H,d,J=4.8Hz),
3.74(4H,t,J=4.4Hz), 4.11(1H,d,J=7.3Hz), 4.18(1H,d,J=8.8Hz),
4.29(1H,d,J=8.8Hz), 4.71(1H,s), 4,86(1H,br s),
5.04(1H,t like,J=5.4Hz), 5.24(1H,d,J=7.3Hz), 5.37(1H,d,J=8.8Hz),
5.44(1H,d,J=8.8Hz), 5.98-6.09(2H,m), 6.31(1H,d,J=2.9Hz),
6.34(1H,dd,J=2.9Hz,J=1.4Hz), 7.36(1H,d,J=1.4Hz), 7.48(2H,t,J=7.8Hz),
7.61(1H,t,J=7.8Hz), 8.06(2H,d,J=7.8Hz).
FAB mass：921(MH+)
【０３４３】
実施例６５
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチンIII
【０３４４】
融点；160-163 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.00-2.30(11H,m), 1.26(3H,s), 1.38(9H,s), 1.42(3H,s), 1.46(6H,s),
1.56(3H,s), 1.61(6H,s), 2.91(1H,d,J=4.0Hz), 4.10(1H,d,J=7.3Hz),
4.22(1H,d,J=8.8Hz), 4.27(1H,d,J=8.8Hz), 4.80-4.90(2H,m),
5.00(1H,d,J=9.8Hz), 5.52(1H,d,J=7.3Hz), 5.90(1H,d,J=9.8Hz),
6.01(1H,d,J=4.0Hz), 6.15-6.25(1H,m), 7.36(2H,d,J=5.3Hz),
7.48(2H,t,J=7.3Hz), 7.61(1H,t,J=7.3Hz), 8.05(2H,d,J=7.3Hz),
8.56(2H,d,J=5.3Hz).
FAB mass：875(MH+)
【０３４５】
実施例６６
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(2-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３４６】
融点；151-153 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.15(4H,m), 1.30(3H,s), 1.39(3H,s), 1.42(9H,s), 1.51(3H,s),
1.57(6H,s), 1.63(3H,s), 1.66(3H,s), 2.09-2.42(5H,m),
2.92(1H,d,J=4.9Hz), 3.82(1H,m), 4.04(1H,m),
4.34(2H,AB type q,J=7.8Hz), 4.76(1H,d,J=8.3Hz), 5.10(1H,s),
5.11(1H,d,J=10.3Hz), 5.48(1H,d,J=7.3Hz), 6.04(1H,d,J=4.9Hz),
6.16(1H,t,J=8.3Hz), 7.23(1H,t,J=4.4Hz), 7.42(1H,d,J=7.8Hz),
7.49(2H,t,J=7.8Hz), 7.61(1H,t,J=7.3Hz), 7.72(1H,t,J=6.8Hz),
8.07(2H,d,J=7.3Hz), 8.46(1H,d,J=4.4Hz).
FAB mass：891(MH+).
【０３４７】
実施例６７
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-10- デアセチル-7- デオキシ-9,10-Ｏ- エチリデン-9- ジヒドロバッカチンIII
【０３４８】
融点；104-106 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.20-2.10(5H,m), 1.25(3H,s), 1.42(9H,s), 1.49(3H,d,J=4.8Hz),
1.50(3H,s), 1.62(3H,s), 1.74(3H,s), 2.30-2.50(1H,m), 2.32(3H,s),
2.93(1H,d,J=4.8Hz), 4.12(1H,d,J=7.4Hz), 4.24(1H,d,J=8.8Hz),
4.29(1H,br), 4.33(1H,d,J=8.8Hz), 4.72(1H,d,J=2.0Hz), 4.92(1H,s),
5.06(1H,q,J=4.8Hz), 5.25(1H,d,J=8.3Hz), 5.39(1H,d,J=10.0Hz),
5.44(1H,d,J=10.0Hz), 6.01(1H,d,J=4.8Hz), 6.05-6.20(1H,m),
6.31(1H,d,J=2.9Hz), 6.35(1H,dd,J=2.9Hz,J=1.9Hz), 7.22(1H,s like),
7.47(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.13(2H,d,J=7.8Hz).
FAB mass：810(MH+)
【０３４９】
実施例６８
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３５０】
融点；140-143 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.20-2.20(5H,m), 1.25(3H,s), 1.41(9H,s), 1.48(3H,s), 1.63(3H,s),
2.27(3H,s), 2.37(1H,dd,J=15.1Hz,J=5.3Hz), 2.90(1H,d,J=4.4Hz),
4.15(1H,d,J=7.3Hz), 4.23(1H,d,J=8.3Hz), 4.31(1H,d,J=8.3Hz),
4.50(1H,s like), 4.62(1H,s like), 4.91(1H,s), 5.20-5.40(2H,m),
5.23(1H,d,J=5.9Hz), 5.46(1H,d,J=10.2Hz), 5.57(1H,d,J=17.6Hz),
5.71(1H,d,J=9.8Hz), 5.90-6.20(3H,m), 7.20-7.50(7H,m),
7.60(1H,t,J=7.9Hz), 8.11(2H,d,J=7.9Hz). FAB mass：832(MH+)
【０３５１】
実施例６９
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３５２】
融点；138-141 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.23-1.29(4H, m), 1.27(3H, s), 1.39(9H, s), 1.41(3H, s),
1.58(3H, s), 1.63(3H, s), 1.66(3H, s), 1.74(3H, s), 1.85(1H, s),
1.98-2.39(5H, m), 2.94(1H, d, J=4.9Hz), 3.84(1H, d, J=7.3Hz),
4.06(1H, m), 4.30(2H, AB type q, J=8.3Hz), 4.55(1H, br),
4.79(1H, d, J=8.3Hz), 4.88(1H, s), 5.07(1H, s),
5.34(1H, d, J=9.3Hz), 5.55(1H, d, J=6.8Hz), 5.83(1H, d, J=9.8Hz),
6.05(2H, m), 7.22(1H, dd,J=7.3Hz, J=4.9Hz), 7.41(1H, d, J=7.8Hz),
7.47(2H, t, J=7.8Hz), 7.60(1H, t, J=7.3Hz), 7.71(1H, t, J=6.4Hz),
8.05(2H,d,J=6.8Hz), 8.50(1H,d,J=4.4Hz).
FAB mass：877(MH+).
【０３５３】
実施例７０
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチンIII
【０３５４】
融点；155-157 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.00-1.20(2H,m), 1.20-1.50(2H,m), 1.22(3H,s), 1.43(9H,s),
1.47(3H,s), 1.50-2.10(6H,m), 1.56(6H,s), 1.60(6H,s),
2.35(1H,t like,J-10.8Hz), 2.87(1H,d,J=4.4Hz), 4.11(1H,d,J=7.4Hz),
4.20(1H,d,J=8.8Hz), 4.27(1H,d,J=8,8Hz), 4.59(1H,s), 4.87(1H,s),
5.28(1H,d,J=8.8Hz), 5.56(1H,d,J=7.4Hz), 5.84(1H,d,J=8.8Hz),
5.95-6.10(2H,m), 7.36(2H,d,J=5.9Hz), 7.47(2H,t,J=7.8Hz),
7.61(1H,t,J=7.8Hz), 8.04(2H,d,J=7.8Hz), 8.58(2H,d,J=5.9Hz).
FAB mass：861(MH+)
【０３５５】
実施例７１
7 α,9β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-7- フルオロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
【０３５６】
融点：139-142.5 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.17(3H,s), 1.40(9H,s), 1.58(3H,s), 1.63(6H,s), 1.82(1H,s),
2.08-2.35(2H,m), 2.28(3H,s), 2.37(1H,dd,J=9.8,J=15.1Hz),
2.40-2.55(1H,m), 2.55-2.67(4H,m), 2.85(1H,dd,J=4.4,J=13.7Hz),
2.89(1H,dd,J=4.4,J=13.7Hz), 3.48(1H,d,J=5.2Hz), 3.74(4H,t,J=4.6Hz),
4.10-4.28(1H,br), 4.18(1H,d,J=8.3Hz), 4.25(1H,d,J=8.3Hz),
4.38(1H,d,J=8.3Hz), 4.61(1H,br s), 4.75(1H,br d,J=46.4Hz),
4.91(1H,t,J=4.4Hz), 4.95(1H,br d,J=5.9Hz), 5.31(1H,br d,J=9.1Hz),
5.37(1H,d,J=8.3Hz), 5.66(1H,br d,J=9.1Hz), 5.90(1H,d,J=5.2Hz),
6.07(1H,br t,J=8.3Hz), 7.28(1H,t,J=7.3Hz), 7.35(2H,t,J=7.3Hz),
7.41(2H,d,J=7.3Hz), 7.48(2H,t,J=7.8Hz), 7.61(1H,t,J=7.8Hz),
8.09(2H,d,J=7.8Hz)
FAB mass : 923(MH+)
【０３５７】
実施例７２
7 α,9β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-7- フルオロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３５８】
融点：154-158 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.19(3H,s), 1.41(9H,s), 1.42(3H,s), 1.56(3H,s), 1.61(3H,s),
1.62(3H,s), 1.63(3H,s), 1.87(1H,s), 2.32(3H,s), 2.08-2.47(4H,m),
3.46(1H,d,J=5.4Hz), 4.28-4.40(1H,br), 4.31(1H,d,J=8.5Hz),
4.36(1H,d,J=8.5Hz), 4.59(1H,d,J=8.6Hz), 4.63(1H,br s),
4.87(1H,ddd,J=3.9,J=7.8,J=45.9Hz), 4.93-4.97(1H,m),
5.31(1H,br d,J=9.6Hz), 5.52(1H,d,J=8.6Hz), 5.69(1H,br d,J=9.6Hz),
5.92(1H,d,J=5.4Hz), 6.12(1H,br t,J=8.3Hz), 7.35(2H,d,J=6.2Hz),
7.48(2H,t,J=7.6Hz), 7.62(1H,t,J=7.6Hz), 8.10(2H,d,J=7.6Hz),
8.60(2H,d,J=6.2Hz)
FAB mass : 853(MH+)
【０３５９】
実施例７３
7 α,9β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-7- フルオロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
【０３６０】
融点：134-138.5 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.19(3H,s), 1.41(9H,s), 1.57(3H,s), 1.63(3H,s), 1.72(3H,s),
1.81(1H,s), 2.10-2.50(4H,m), 2.33(3H,s), 2.50-2.75(4H,m),
2.82-2.93(2H,m), 3.49(1H,d,J=5.2Hz), 3.75(4H,t,J=4.6Hz),
4.00(1H,br s), 4.21(1H,br d,J=8.8Hz), 4.26(1H,d,J=8.3Hz),
4.49(1H,d,J=8.3Hz), 4.71(1H,br s), 4.76(1H,br d,J=46.5Hz),
4.91(1H,t,J=4.2Hz), 4.96(1H,br d,J=6.4Hz), 5.33-5.42(3H,m),
5.91(1H,d,J=5.2Hz), 6.10(1H,br t,J=8.3Hz), 6.32(1H,d,J=2.9Hz),
6.34-6.38(1H,m), 7.38(1H,br s), 7.49(2H,t,J=7.3Hz),
7.61(1H,t,J=7.3Hz), 8.10(2H,d,J=7.3Hz)
FAB mass : 913(MH+)
【０３６１】
実施例７４
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０３６２】
融点；146-149 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.40(9H,s), 1.46(3H,s), 1.59(3H,s), 1.60-2.10(5H,m),
2.27(3H,s), 2.30-2.45(1H,m), 2.58-2.94(6H,m), 2.90(1H,d,J=4.4Hz),
3.74(4H,t,J=4.8Hz), 4.09(1H,d,J=7.4Hz), 4.23(1H,d,J=8.8Hz),
4.31(1H,d,J=8.8Hz), 4.50(1H,br), 4.62(1H,s), 4.91(1H,s),
5.04(1H,t,J=3.9Hz), 5.22(1H,d,J=7.4Hz), 5.31(1H,d,J=9.3Hz),
5.70(1H,d,J=9.3Hz), 6.05(1H,d,J=4.4Hz), 6.05-6.18(1H,m),
7.20-7.48(7H,m), 7.60(1H,t,J=7.3Hz), 8.11(2H,d,J=7.3Hz).
FAB mass：905(MH+)
【０３６３】
実施例７５
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-9,10-Ｏ- エチリデン-9- ジヒドロバッカチンIII
【０３６４】
融点；120-122 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.10-2.10(5H,m), 1.23(3H,s), 1.25(3H,s), 1.42(9H,s),
1.49(3H,d,J=5.3Hz), 1.57(3H,s), 1.61(3H,s), 2.20-2.40(1H,m),
2.26(3H,s), 2.90(1H,d,J=4.9Hz), 4.08(1H,d,J=7.3Hz),
4.25(1H,d,J=8.8Hz), 4.32(1H,d,J=8.8Hz), 4.62(1H,s), 4.80-5.00(2H,m),
5.06(1H,q,J=5.3Hz), 5.22(1H,d,J=7.3Hz), 5.32(1H,d like,J=9.3Hz),
5.79(1H,d like,J=9.3Hz), 6.03(1H,d,J=4.9Hz), 6.05-6.20(1H,m),
7.38(2H,d,J=4.8Hz), 7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.11(2H,d,=7.8Hz), 8.61(2H,d,J=4.8Hz).
FAB mass：821(MH+)
【０３６５】
実施例７６
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-エチル-2- ヒドロキシ-3-(4-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３６６】
融点；125-164 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.95(3H,t,J=6.8Hz), 1.11-1.48(6H,m), 1.25(6H,s), 1.29(3H,s),
1.66(3H,s), 1.90-2.37(5H,m), 2.89(1H,d,J=4.4Hz),
3.71(1H,d,J=7.3Hz), 4.06(1H,m), 4.31(2H,s),
4.67(1H,d,J=8.3Hz), 5.01(1H,d,J=9.8Hz), 5.05(1H,s),
5.45(1H,d,J=6.8Hz), 5.91(1H,d,J=9.8Hz), 6.07(1H,d,J=4.4Hz),
6.21(1H,t,J=8.0Hz), 7.36(2H,d,J=5.9Hz), 7.49(2H,t,J=7.3Hz),
7.62(1H,t,J=7.3Hz), 8.04(2H,d,J=8.3Hz), 8.56(2H,d,J=5.4Hz).
FAB mass：905(MH+).
【０３６７】
実施例７７
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３６８】
融点；133-136 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.42(9H,s), 1.49(3H,s), 1.63(3H,s), 1.75(3H,s),
1.80-2.15(5H,m), 2.30-2.44(1H,m), 2.33(3H,s), 2.93(1H,d,J=4.9Hz),
4.17(1H,d,J=6.8Hz), 4.23(1H,d,J=8.8Hz), 4.33(1H,d,J=8.8Hz),
4.72(1H,s), 4.92(1H,s), 5.24(1H,d,J=6.3Hz), 5.30(1H,d,J=6.8Hz),
5.38(1H,d,J=10.2Hz), 5.42-5.54(2H,m), 5.58(1H,d,J=17.5Hz),
5.96-6.08(2H,m), 6.11(1H,t,J=7.9Hz), 6.31(1H,d,J=3.4Hz),
6.34(1H,dd,J=3.4Hz,J=1.9Hz), 7.39(1H,s like), 7.47(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz).
FAB mass：822(MH+)
【０３６９】
実施例７８
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-エチル-2- ヒドロキシ-3-(4-ピリジル) プロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３７０】
融点；161-163 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.95(3H,t,J=7.3Hz), 1.26(3H,s), 1.30(3H,s), 1.36(9H,s),
1.39(3H,s), 1.57(3H,s), 1.62(3H,s), 1.67(3H,s),
1.82-2.35(4H,m), 2.49(3H,s), 2.89(1H,d,J=4.4Hz),
3.75(1H,d,J=7.3Hz), 4.06(1H,br), 4.38(2H,s),
4.67(1H,d,J=7.8Hz), 5.01(1H,d,J=9.8Hz), 5.10(1H,s),
5.45(1H,d,J=6.8Hz), 5.82(1H,brd,J=9.3Hz), 6.04(1H,d,J=4.4Hz),
6.24(1H,t,J=8.0Hz), 7.36(2H,d,J=5.4Hz), 7.48(2H,t,J=7.8Hz),
7.60(1H,t,J=7.3Hz), 8.24(2H,d,J=7.3Hz), 8.56(2H,d,J=5.4Hz).
FAB mass：879(MH+).
【０３７１】
実施例７９
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０３７２】
融点；140-143 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.41(9H,s), 1.47(3H,s), 1.60(3H,s), 1.60-2.15(5H,m),
1.73(3H,s), 2.20-2.42(1H,m), 2.32(3H,s), 2.52-2.84(6H,m),
2.92(1H,d,J=4.9Hz), 3.74(4H,t,J=4.4Hz), 4.11(1H,d,J=6.9Hz),
4.23(1H,d,J=8.3Hz), 4.32(1H,d,J=8.3Hz), 4.72(1H,s), 4.91(1H,s),
5.04(1H,t,J=3.9Hz), 5.24(1H,d,J=6.9Hz), 5.45(1H,d,J=9.3Hz),
5.99(1H,d,J=4.9Hz), 6.03-6.18(1H,m), 6.31(1H,s like),
6.34(1H,s like), 7.38(1H,s like), 7.47(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz).
FAB mass：895(MH+)
【０３７３】
実施例８０
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチンIII
【０３７４】
融点；145-148 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.43(3H,s), 1.44(9H,s), 1.52(3H,s), 1.56(3H,s),
1.61(3H,s), 1.71(3H,s), 1.80-2.20(4H,m), 2.22-2.31(2H,m),
2.35(3H,s), 2.94(1H,d,J=4.9Hz), 4.17(1H,d,J=7.3Hz),
4.23(1H,d,J=8.3Hz), 4.32(1H,d,J=8.3Hz), 4.88(1H,d,J=2.5Hz),
4.92(1H,s), 5.34(1H,d,J=9.3Hz), 5.56(1H,d,J=7.3Hz),
5.94(1H,d,J=9.3Hz), 5.96(1H,d,J=4.9Hz), 6.09(1H,t,J=8.3Hz),
7.22(1H,dd,J=7.3Hz,J=4.9Hz), 7.38-7.50(3H,m), 7.59(1H,t,J=7.8Hz),
7.72(1H,t,J=7.3Hz), 8.12(2H,d,J=7.8Hz), 8.54(1H,d,J=4.4Hz).
FAB mass：835(MH+)
【０３７５】
実施例８１
7 α,9β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-7-デオキシ-4,10-ジデアセチル-9- ジヒドロ-7- フルオロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
【０３７６】
融点：124.5-129.5 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.02(3H,t,J=7.3Hz), 1.19(3H,s), 1.40(9H,s), 1.57(3H,s), 1.63(3H,s),
1.72(3H,s), 1.81(1H,s), 1.75-1.90(2H.m), 2.15-2.55(6H,m),
2.55-2.67(4H,m), 2.82-2.93(2H,m), 3.49(1H,d,J=5.4Hz),
3.74(4H,t,J=5.1Hz), 3.92(1H,br s), 4.22(1H,d,J=8.3Hz),
4.27(1H,d,J=8.3Hz), 4.39(1H,d,J=8.3Hz), 4.66-4.73(1H,br),
4.68-4.85(1H,m), 4.87-4.95(2H,m), 5.30-5.41(3H,m),
5.91(1H,d,J=5.4Hz), 6.08(1H,br t,J=8.1Hz), 6.33(1H,d,J=3.4Hz),
6.36(1H,dd,J=3.4,J=1.5Hz), 7.39(1H,d,J=1.5Hz), 7.48(2H,t,J=7.8Hz),
7.62(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz)
【０３７７】
実施例８２
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(2-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチンIII
【０３７８】
融点；147-150 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.29(3H,s), 1.40(3H,s), 1.42(9H,s), 1.52(3H,s), 1.54(3H,s),
1.55(6H,s), 1.61(3H,s), 1.80-2.23(6H,m), 2.51(3H,s),
2.94(1H,d,J=4.9Hz), 4.18(1H,d,J=7.3Hz), 4.22(1H,d,J=7.3Hz),
4.34(1H,d,J=8.3Hz), 4.94(1H,s), 5.10(1H,d,J=10.2Hz),
5.49(1H,d,J=7.3Hz), 6.03(1H,d,J=10.2Hz), 6.15(1H,t,J=8.8Hz),
7.18-7.33(1H,m), 7.37-7.55(3H,m), 7.60(1H,t,J=7.4Hz),
7.67-7.80(1H,m), 8.15(2H,d,J=7.4Hz), 8.49(1H,d,J=4.4Hz).
FAB mass：849(MH+)
【０３７９】
実施例８３
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-4- Ｏ- プロピオニルバッカチン III
【０３８０】
融点；148-150 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.28(3H,s), 1.32(3H,t,J=7.5Hz), 1.40(3H,s), 1.44(9H,s), 1.58(3H,s),
1.65(3H,s), 1.66(3H,s), 2.18(2H,br), 2.27(1H,m), 2.68(2H,q,J=7.5Hz),
2.96(1H,d,J=4.9Hz), 3.88(1H,d,J=7.3Hz), 4.06(1H,m),
4.32(1H,d,J=8.3Hz), 4.41(1H,d,J=8.3Hz), 4.68(1H,d,J=7.8Hz),
4.85(1H,br), 5.05(1H,t-br), 5.32(1H,m), 5.52(1H,d,J=7.3Hz),
5.87(1H,d,J=9.9Hz), 6.03(1H,d,J=4.9Hz), 6.09(1H,t,J=8.8Hz),
7.24(1H,m), 7.42(1H,d,J=7.8Hz), 7.47(2H,t,J=7.5Hz),
7.60(1H,t,J=7.5Hz), 7.73(1H,td,J=7.8Hz,J=2Hz), 8.13(2H,m),
8.52(1H,d,J=4.4Hz).
FAB mass：866(MH+)
【０３８１】
実施例８４
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(2-ピリジル) プロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３８２】
融点；145-151 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.29(3H,s), 1.38(3H,s), 1.44(9H,s), 1.50(3H,s), 1.55(3H,s),
1.56(3H,s), 1.64(3H,s), 1.66(3H,s), 2.07-2.30(4H,m),
2.55(3H,s), 2.94(1H,d,J=5.4Hz), 3.86(1H,d,J=7.3Hz), 4.05(1H,m),
4.36(2H,AB type q,J=8.3Hz), 4.69(1H,d,J=7.8Hz), 5.10(1H,d,J=10.3Hz),
5.11(1H,s like), 5.45(1H,d,J=7.8Hz), 5.99-6.03(2H,m),
6.16(1H,t,J=9.3Hz), 7.24(1H,m), 7.43-7.48(3H,m),
7.60(1H,t,J=7.3Hz), 7.73(1H,t,J=6.8Hz), 8.14(2H,d,J=7.8Hz),
8.47(1H,d,J=4.4Hz).
FAB mass：865(MH+).
【０３８３】
実施例８５
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(2-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-4- Ｏ- プロピオニルバッカチン III
【０３８４】
融点；147-150 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(s), 1.38(s), 1.40(3H,t,J=7.3Hz), 1.44(9H,s), 1.50(s), 1.55(s),
1.57(s), 1.64(s), 1.65(s), 2.12(1H,dd,J=14.7Hz,J=8.8Hz),
2.20(2H,t,J=3.4Hz), 2.29(1H,dd,J=14.7Hz,J=8.8Hz), 2.88(2H,q,J=7.5Hz),
2.94(1H,d,J=5.4Hz), 3.88(1H,d,J=7.3Hz), 4.05(1H,m),
4.32(1H,d,J=8.3Hz), 4.44(1H,d,J=8.3Hz), 4.67(1H,d,J=7.8Hz),
5.07(1H,m), 5.45(1H,d,J=7.3Hz), 6.01(2H,m), 6.14(1H,t,J=9Hz),
7.24(1H,m), 7.44(1H,d,J=8.3Hz), 7.48(2H,t,J=7.8Hz),
7.60(1H,t,J=7.3Hz), 7.73(1H,td,J=7.5Hz,J=1.5Hz), 8.14(2H,m),
8.47(1H,d,J=4.4Hz).
FAB mass：879(M+).
【０３８５】
実施例８６
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-ピリジル) プロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０３８６】
融点；150-153 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H, s), 1.40(3H, s), 1.44(9H, s), 1.58(3H, s), 1.64(3H, s),
1.66(3H, s), 1.69(3H, s), 2.05-2.32(4H, m), 2.40(3H, s),
2.95(1H, d, J=4.9Hz), 3.86(1H, d, J=7.8Hz), 4.06(1H, m),
4.35(2H, AB type q, J=8.3Hz), 4.70(d, J=8.3Hz), 4.85(1H, d, J=2.4Hz),
5.11(1H, s), 5.35(1H. d, J=9.3Hz), 5.53(1H, d, J=7.3Hz),
5.90(1H,d,J=9.8Hz), 6.03(1H,d,J=5.4Hz), 6.10(1H,t,J=8.3Hz),
7.24(1H,m), 7.41(1H,d,J=7.8Hz), 7.47(2H,t,J=7.8Hz),
7.59(1H,t,J=7.3Hz), 7.73(1H,t,J=5.9Hz), 8.11(2H,d,J=8.8Hz),
8.52(1H,d,J=4.9Hz).
FAB mass：852(MH2 +).
【０３８７】
実施例８７
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(2-ピリジル) プロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
【０３８８】
融点；140-145 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(3H,s), 1.44(9H,s), 1.52(3H,s), 1.54(3H,s), 1.62(3H,s),
1.68(3H,s), 2.13-2.30(4H,m), 2.55(3H,s), 2.95(1H,d,J=4.9Hz),
3.89(1H,d,J=6.8Hz), 4.08(1H,m), 4.35(2H,AB type q,J=8.3Hz),
4.61(1H,d,J=8.3Hz), 5.12(3H,m), 5.19(1H,d,J=6.4Hz),
5.45(1H,d,J=10.7Hz), 5.56(1H,d,J=17.6Hz), 6.01(2H,m),
6.17(2H,m), 7.24(1H,m), 7.43-7.51(3H,m), 7.61(1H,t,J=7.3Hz),
7.73(1H,t,J=6.4Hz), 8.13(2H,d,J=7.3Hz), 8.48(1H,d,J=4.4Hz).
FAB mass：864(MH2 +).
【０３８９】
実施例８８
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(2-ピリジル) プロピオニル]-10- デアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
【０３９０】
融点;135-139℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(3H,s), 1.43(9H,s), 1.51(3H,s), 1.54(3H,s), 1.61(3H,s),
1.64(3H,s), 2.09-2.34(4H,m), 2.55(3H,s), 2.62(4H,m),
2.77(2H,AB type dq,J=26.9Hz,J=3.4Hz), 2.95(1H,d,J=4.9Hz),
3.73(4H,t like,4.9Hz), 3.81(1H,d,J=7.3Hz), 4.07(1H,m),
4.35(2H,AB type q,J=8.3Hz), 4.71(1H,d,J=8.3Hz), 4.99(1H,t,J=4.4Hz),
5.10(1H,d,J=10.3Hz), 5.12(1H,d,J=7.3Hz), 6.01(1H,d,J=5.4Hz),
6.02(1H,d,J=4.9Hz), 6.16(1H,t,J=7.8Hz), 7.23(1H,m),
7.43(1H,d,J=7.8Hz), 7.49(2H,t,J=7.8Hz), 7.61(1H,t,J=7.8Hz),
7.73(1H,t,J=7.8Hz), 8.13(2H,d,J=7.3Hz), 8.47(1H,d,J=4.9Hz).
FAB mass：936(MH+).
【０３９１】
実施例８９
9 β-13-Ｏ-[(2R,3S)-3-( ベンゾイルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３９２】
融点；150-153 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.05-1.13(2H,m), 1.21(3H,s), 1.38-1.50(2H,m), 1.43(3H,s),
1.46(3H,s), 1.55-1.75(2H,m), 1.60(3H,s), 1.78-2.11(5H,m),
2.38(1H,dd,J=15.1Hz,J=9.7Hz), 2.85(1H,d,J=4.9Hz),
4.09(1H,d,J=6.9Hz), 4.18(1H,d,J=8.8Hz), 4.27(1H,d,J=8.8Hz),
4.73(1H,s like), 4.88(1H,s like), 4.93(1H,s like), 5.18-5.27(2H,m),
5.44(1H,d,J=10.3Hz), 5.55(1H,d,J=17.1Hz),
5.85(1H,dd,J=9.3Hz,J=2.5Hz), 5.94-6.09(3H,m), 7.24-7.57(11H,m),
7.60(1H,t,J=7.3Hz), 7.84(2H,d like,J=8.3Hz), 8.04(2H,d,J=7.3Hz).
FAB mass：862(MH+)
【０３９３】
実施例９０
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-4- Ｏ- プロピオニルバッカチン III
【０３９４】
融点；152-155 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.30(s), 1.38(s), 1.40(s), 1.41(s), 1.44(s), 1.58(s), 1.68(s),
2.06(1H,m), 2.10(1H,m), 2.22(1H,m), 2.26(1H,m), 2.63(1H,m),
2.75(1H,m), 2.91(1H,d,J=4.4Hz), 3.78(1H,d,J=7.8Hz), 4.08(1H,br),
4.39(2H,AB type q,J=8.8Hz), 4.70(1H,d,J=7.8Hz), 4.99(1H,d,J=9.8Hz),
5.48(1H,d,J=7.3Hz), 5.78(1H,d,J=9.8Hz), 6.06(1H,d,J=4.3Hz),
6.21(1H,t-br), 7.35(2H,d,J=5Hz), 7.48(2H,t,J=7.8Hz),
7.61(1H,t,J=7.3Hz), 8.14(2H,m), 8.59(2H,d,J=5Hz).
FAB mass：879(M+).
【０３９５】
実施例９１
9 β-13-Ｏ-[(2R,3S)-3-( ベンゾイルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０３９６】
融点；150-153 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.04-1.13(2H,m), 1.21(3H,s), 1.36-1.47(2H,m), 1.42(3H,s),
1.44(3H,s), 1.53-2.08(7H,m), 1.57(3H,s),
2.37(1H,dd,J=15.1Hz,J=9.8Hz), 2.53-2.73(5H,m),
2.77(1H,dd,J=13.6Hz,J=3.9Hz), 2.85(1H,d,J=4.4Hz),
3.73(4H,t,J=4.4Hz), 4.17(1H,d,J=6.8Hz), 4.26(1H,d,J=8.8Hz),
4.30(1H,d,J=8.8Hz), 4.73(1H,d,J=2.4Hz), 4.87(1H,br s),
5.00(1H,t,J=4.4Hz), 5.14(1H,d,J=6.8Hz), 5.85(1H,dd,J=9.3Hz,J=2.5Hz),
5.97-6.06(2H,m), 7.23-7.56(10H,m), 7.60(1H,t,J=7.3Hz),
7.84(1H,d,J=7.3Hz), 8.04(2H,d,J=7.3Hz).
FAB mass：935(MH+)
【０３９７】
実施例９２
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4-Ｏ- エトキシカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０３９８】
融点；117-120 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.34(3H,t,J=7.4Hz), 1.40(9H,s), 1.62(3H,s),
1.65(3H,br s), 1.67(3H,s), 1.88(1H,s), 1.99-2.29(3H,m),
2.47(1H,dd,J=15.1Hz,J=9.7Hz), 2.86(1H,d,J=4.3Hz),
3.87(1H,d,J=6.8Hz), 3.97(1H,br), 4.08(1H,m), 4.30-4.66(6H,m),
5.17-5.36(3H,m), 5.45(1H,d,J=10.8Hz), 5.57(1H,d,J=17.1Hz),
5.66(1H,d,J=9.7Hz), 5.92(1H,br t,J=7.3Hz),
6.03(1H,ddd,J=17.1Hz,J=10.8Hz,J=6.3Hz), 6.11(1H,d,J=4.3Hz),
7.24-7.49(7H,m), 7.58(1H,t,J=7.3Hz), 8.03(2H,d,J=7.3Hz).
FAB mass：878(MH+).
【０３９９】
実施例９３
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- エトキシカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０４００】
融点；121-123 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.37(3H,t,J=6.9Hz), 1.38(9H,s), 1.63(3H,s), 1.68(3H,s),
1.75(3H,s), 1.88(1H,s), 2.02-2.12(1H,m), 2.18-2.37(2H,m),
2.45(1H,dd,J=15.2Hz,J=9.8Hz), 2.88(1H,d,J=4.9Hz), 3.80-3.94(2H,m),
4.08(1H,br), 4.29-4.61(5H,m), 4.70(1H,s like), 5.18-5.29(2H,m),
5.29(1H,d,J=7.0Hz), 5.30-5.45(2H,m), 5.46(1H,d,J=10.7Hz),
5.57(1H,d,J=17.0Hz), 5.97-6.15(2H,m), 6.10(1H,d,J=4.9Hz),
7.38(1H,s like), 7.44(2H,t,J=7.8Hz), 7.58(1H,t,J=7.8Hz),
8.05(2H,d,J=7.8Hz).
FAB mass：868(MH+).
【０４０１】
実施例９４
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-4-Ｏ- エトキシカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０４０２】
融点；128-131 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.33(3H,t,J=7.3Hz), 1.40(9H,s), 1.60(3H,s), 1.64(6H,s),
1.86(1H,s), 2.00-2.09(1H,m), 2.14-2.30(2H,m),
2.46(1H,dd,J=15.1Hz,J=9.7Hz), 2.56-2.71(4H,m),
2.75(1H,dd,J=13.6Hz,J=5.3Hz), 2.80-2.91(2H,m), 3.73(4H,t,J=5.3Hz),
3.78(1H,d,J=7.3Hz), 4.06(1H,br), 4.29-4.48(3H,m), 4.50-4.68(3H,m),
5.03(1H,t like,J-5.3Hz), 5.19-5.35(3H,m), 5.65(1H,d,J=9.8Hz),
5.92(1H,br t,J=6.8Hz), 6.09(1H,d,J=4.4Hz), 7.25-7.50(7H,m),
7.59(1H,t,J=7.8Hz), 8.03(2H,d,J=7.8Hz).
FAB mass：951(MH+).
【０４０３】
実施例９５
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチンIII
【０４０４】
融点；182-184 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H,s), 1.37(9H,s), 1.42(6H,s), 1.47(3H,br s), 1.50(3H,s),
1.56(3H,s), 1.62(3H,s), 1.75-2.11(6H,m),
2.22(1H,dd,J=14.2Hz,J=10.2Hz), 2.30-2.50(1H,m), 2.42(3H,s),
2.91(1H,d,J=4.4Hz), 4.12(1H,d,J=7.3Hz), 4.28(1H,d,J=8.3Hz),
4.32(1H,d,J=8.3Hz), 4.58(1H,br), 4.92(1H,s), 5.00(1H,d,J=10.2Hz),
5.51(1H,d,J=7.3Hz), 5.92(1H,d,J=10.2Hz), 5.98(1H,d,J=4.4Hz),
6.17-6.29(1H,m), 7.36(2H,d,J=5.4Hz), 7.47(2H,t,J=7.9Hz),
7.60(1H,t,J=7.9Hz), 8.13(2H,d,J=7.9Hz), 8.58(2H,d,J=5.4Hz).
FAB mass：849(MH+).
【０４０５】
実施例９６
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- エトキシカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０４０６】
融点；130-132 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.26(3H,s), 1.36(3H,t,J=6.8Hz), 1.41(9H,s), 1.61(3H,s), 1.65(3H,s),
1.73(3H,s), 1.85(1H,s), 2.00-2.10(1H,m), 2.19-2.39(2H,m),
2.42(1H,dd,J=15.1Hz,J=9.8Hz), 2.54-2.93(7H,m), 3.73(4H,t,J=4.4Hz),
3.80(1H,d,J=7.3Hz), 4.06(1H,br), 4.25-4.50(3H,m),
4.53(1H,d,J=8.8Hz), 4.61(1H,d,J=7.8Hz), 4.70(1H,s),
5.03(1H,t,J=4.4Hz), 5.17-5.45(4H,m), 5.99(1H,t,J=7.8Hz),
6.08(1H,d,J=4.4Hz), 6.28-6.42(2H,m), 7.38(1H.s like),
7.45(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.05(2H,d,J=7.8Hz).
FAB mass：941(MH+).
【０４０７】
実施例９７
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-チエニル) プロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０４０８】
融点；135-137 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.41(9H,s), 1.48(3H,s), 1.63(3H,s), 1.66(3H,s),
1.80-2.22(5H,m), 2.31(3H,s), 2.37(1H,dd,J=15.1Hz,J=10.2Hz),
2.92(1H,d,J=5.3Hz), 4.16(1H,d,J=6.9Hz), 4.24(1H,d,J=8.8Hz),
4.33(1H,d,J=8.8Hz), 4.57(1H,s), 4.64(1H,s), 4.93(1H,s),
5.23(1H,d,J=6.4Hz), 5.29(1H,d,J=6.9Hz), 5.46(1H,d,J=10.8Hz),
5.50-5.74(3H,m), 5.96-6.18(3H,m), 6.98(1H,dd,J=5.4Hz,J=4.0Hz),
7.10(1H,d,J=4.0Hz), 7.22-7.27(1H,m), 7.47(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz).
FAB mass：838(MH+).
【０４０９】
実施例９８
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-チエニル) プロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０４１０】
融点；135-138 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.41(9H,s), 1.47(3H,s), 1.59(3H,s), 1.60-2.15(5H,m),
1.65(3H,s), 2.31(3H,s), 2.36(1H,dd,J=15.2Hz,J=9.8Hz),
2.57-2.86(6H,m), 2.91(1H,d,J=4.9Hz), 3.74(4H,t,J=4.8Hz),
4.10(1H,d,J=6.8Hz), 4.23(1H,d,J=8.3Hz), 4.32(1H,d,J=8.3Hz),
4.64(1H,s), 4.92(1H,s), 5.04(1H,t,J=3.9Hz), 5.22(1H,d,J=6.8Hz),
5.54(1H,d,J=9.8Hz), 5.60(1H,d,J=9.8Hz), 5.99(1H,d,J=4.9Hz),
6.08(1H,t,J=7.8Hz), 6.97(1H,dd,J=5.3Hz,J=3.4Hz), 7.10(1H,d,J=3.4Hz),
7.20-7.20(1H,m), 7.47(2H,t,J=7.8Hz), 7.61(1H,t,J=7.8Hz),
8.12(2H,d,J=7.8Hz).
FAB mass：911(MH+).
【０４１１】
実施例９９
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-4- Ｏ- エトキシカルボニル-9,10-Ｏ- イソプロピリデンバッカチン III
【０４１２】
融点；131-135 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.37(3H,t,J=7.3Hz), 1.41(3H,s), 1.45(9H,s),
1.59(3H,s), 1.65(6H,s), 1.74(3H,s), 1.87-2.39(1H,d,J=4.4Hz),
2.86(1H,d,J=4.4Hz), 3.63(1H,d,J=7.3Hz), 4.04(1H,m),
4.34(2H,m), 4.48(1H,q,J=7.3Hz), 4.53(1H,d,J=8.8Hz),
4.67(1H,d,J=7.8Hz), 4.80(1H,d,J=2.8Hz), 5.23(1H,d,J=7.8Hz),
5.57(1H,d,J=7.3Hz), 5.59(2H,m), 6.07(1H,d,J=4.9Hz),
7.24(1H,dd,J=7.3Hz,J=4.9Hz), 7.45(2H,t,J=7.8Hz),
7.58(1H,t,J=7.3Hz), 7.73(1H,dt,J=7.8Hz,J=2.0Hz),
8.05(2H,d,J=7.2Hz), 8.50(1H,d,J=3.9Hz).
FAB mass：881(MH+).
【０４１３】
実施例１００
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-4- Ｏ- エトキシカルボニル-9,10-Ｏ- イソプロピリデンバッカチン III
【０４１４】
融点；132-137 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.23(3H,s), 1.37(3H,t,J=7.3Hz), 1.41(9H,s), 1.59(3H,s),
1.62(3H,s), 1.64(3H,s), 1.66(6H,s), 2.02-2.48(4H,m),
2.87(1H,d,J=4.4Hz), 3.79(1H,d,J=7.3Hz), 4.06(1H,m),
4.35(1H,d,J=8.8Hz), 4.43(2H,q,J=7.3Hz), 4.52(1H,d,J=8.8Hz),
4.62(2H,s), 5.21(1H,s), 5.30(1H,d,J=8.3Hz),
5.66(1H,d,J=7.3Hz), 5.75(1H,d,J=9.8Hz), 5.94(1H,t,J=8.0Hz),
6.12(1H,d,J=4.4Hz), 7.37(2H,d,J=4.9Hz), 7.44(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.03(2H,d,J=7.3Hz), 8.60(2H,d,J=5.4Hz).
FAB mass：881(MH+).
【０４１５】
実施例１０１
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-4- Ｏ- エトキシカルボニル-9,10-Ｏ- イソプロピリデンバッカチン III
【０４１６】
融点；149-153 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.28(3H,s), 1.38(9H,s), 1.41(3H,s), 1.42(3H,s),
1.45(3H,t,J=7.3Hz), 1.53(3H,s), 1.59(3H,s), 1.65(3H,s),
1.67(3H,s), 2.02-2.27(4H,m), 2.91(1H,d,J=3.9Hz),
3.78(1H,d,J=7.3Hz), 4.06(1H,m), 4.53(1H,d,J=8.8Hz),
4.54(3H,m), 4.63(1H,d,7.8Hz), 5.09(1H,d,J=10.3Hz), 5.21(1H,s),
5.53(1H,d,J=7.3Hz), 5.82(1H,d,J=9.8Hz), 6.10(1H,d,J=4.4Hz),
6.17(1H,t,J=8.3Hz), 7.39(2H,d,J=4.9Hz), 7.44(2H,t,J=7.8Hz),
7.59(1H,t,J=7.3Hz), 8.05(2H,d,J=7.3Hz), 8.58(2H,d,J=4.9Hz).
FAB mass：895(MH+).
【０４１７】
実施例１０２
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ- チオカルボネートバッカチンIII
【０４１８】
融点；162-165 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.30(3H,s), 1.40(9H,s), 1.50-2.15(5H,m), 1.61(3H,s),
1.62(3H,s), 2.29(3H,s), 2.41(1H,dd,J=15.2Hz,J=9.8Hz),
2.87(1H,d,J=4.9Hz), 4.10(1H,br), 4.20(1H,d,J=8.8Hz),
4.32(1H,d,J=8.8Hz), 4.63(1H,br), 4.85(1H,d,J=8.7Hz), 4.90(1H,s),
5.28(1H,d,J=9.2Hz), 5.58(1H,d,J=9.2Hz), 5.99(1H,d,J=4.9Hz),
6.04-6.18(2H,m), 7.20-7.45(5H,m), 7.48(2H,t,J=7.8Hz),
7.62(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
FAB mass：836(MH+).
【０４１９】
実施例１０３
7 α,9β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-(2-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-7- フルオロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０４２０】
融点：136-141 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.21(3H,s), 1.42(3H,s), 1.44(9H,s), 1.52(3H,s), 1.59(3H,s),
1.65(3H,s), 1.70(1H,s), 1.74(3H,s), 2.07-2.45(4H,m),
2.27(1H,d,J=9.3Hz), 2.41(3H,s), 3.50(1H,d,J=5.4Hz),
4.29(1H,d,J=8.8Hz), 4.36(1H,d,J=8.8Hz), 4.62(1H,d,J=9.1Hz),
4.84(1H,br s), 4.83-5.02(1H,m), 4.95-5.02(1H,m),
5.36(1H,br d,J=9.8Hz), 5.53(1H,d,J=9.1Hz), 5.86-5.95(2H,m),
6.10(1H,br t,J=8.5Hz), 7.23(1H,dd,J=4.9,J=7.1Hz), 7.41(1H,d,J=7.8Hz),
7.48(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz), 7.73(1H,dt,J=1.5,J=7.8Hz),
8.21(2H,d,J=7.63Hz), 8.46(1H,d,J=4.9Hz)
FAB mass : 853(MH+)
【０４２１】
実施例１０４
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-[2-(1- メチルピペラジン-4- イル) エチリデン] バッカチンIII
【０４２２】
融点；128-130 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.42(9H,s), 1.47(3H,s), 1.58-2.10(6H,m), 1.60(3H,s),
1.73(3H,s), 2.20-2.88(9H,m), 2.32(6H,s), 2.91(1H,d,J=4.9Hz),
4.11(1H,d,J=6.9Hz), 4.23(1H,d,J=8.3Hz), 4.32(1H,d,J=8.3Hz),
4.77(1H,s like), 4.91(1H,s like), 5.03(1H,t,J=3.9Hz),
5.23(1H,d,J=6.9Hz), 5.37(1H,d,J=9.3Hz), 5.43(1H,d,J=9.3Hz),
5.99(1H,d,J=4.9Hz), 6.10(1H,t,J=8.0Hz), 6.31(1H,d,J=3.4Hz),
6.35(1H,dd,J=3.4Hz,J=1.9Hz), 7.39(1H,d,J=1.9Hz), 7.47(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz).
FAB mass：908(MH+).
【０４２３】
実施例１０５
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-ジメチルアミノエチリデン) バッカチンIII
【０４２４】
融点；135-136 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.42(9H,s), 1.47(3H,s), 1.61(3H,s), 1.70-2.10(5H,m),
1.74(3H,s), 2.20-2.35(1H,m), 2.32(3H,s), 2.39(6H,s),
2.67(1H,dd,J=13.2Hz,J=4.9Hz), 2.77(1H,dd,J=13.2Hz,J=4.9Hz),
2.92(1H,d,J=4.8Hz), 4.12(1H,d,J=7.4Hz), 4.23(1H,d,J=8.3Hz),
4.32(1H,d,J=8.3Hz), 4.72(1H,s), 4.92(1H,s), 5.03(1H,t like,J=4.9Hz),
5.25(1H,d,J=7.4Hz), 5.37(1H,d,J=10.3Hz), 5.45(1H,d,J=10.3Hz),
6.00(1H,d,J=4.8Hz), 6.10(1H,t,J=8.3Hz), 6.31(1H,d,J=3.4Hz),
6.35(1H,dd,J=3.4Hz,J=2.1Hz), 7.39(1H,d,J=2.1Hz), 7.47(2H,t,J=7.4Hz),
7.60(1H,t,J=7.4Hz), 8.12(2H,d,J=7.4Hz).
FAB mass：853(MH+).
【０４２５】
実施例１０６
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(2-ピリジル) プロピオニル]-4,10- ジデアセチル-9- ジヒドロ-4- Ｏ- エトキシカルボニル-9,10-Ｏ- イソプロピリデンバッカチン III
【０４２６】
融点；118-122 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H,s), 1.40(3H,s), 1.42(3H,t,J=7.3Hz), 1.45(9H,s),
1.56(3H,s), 1.58(3H,s), 1.64(3H,s), 1.67(3H,s),
2.02-2.48(4H,m), 2.83(1H,d,J=4.9Hz), 3.86(1H,d,J=7.8Hz),
4.09(1H,br), 4.12(1H,d,J=7.3Hz), 4.51(3H,m),
4.64(1H,d,J=7.3Hz), 5.13(1H,d,J=10.3Hz), 5.23(1H,br),
5.51(1H,d,J=9.9Hz), 6.05(2H,m), 7.23(1H,m), 7.45(3H,m),
7.58(1H,t,J=7.3Hz), 7.82(1H,t,J=6.8Hz), 8.06(2H,d,J=7.3Hz),
8.46(1H,m).
FAB mass：895(MH+).
【０４２７】
実施例１０７
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-9- ジヒドロ-9,10-Ｏ-[2-(1- メチルピペラジン-4- イル) エチリデン] バッカチン III
【０４２８】
融点；118-128 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.02(3H,t,J=7.3Hz), 1.28(3H,s), 1.41(9H,s), 1.61(3H,s),
1.65(3H,s), 1.70(3H,s), 1.84(2H,m), 2.03-3.07(20H,m),
3.82(1H,d,J=7.3Hz), 4.08(1H,br), 4.36(2H,AB type q,J=8.3Hz),
4.70(1H,s), 5.01(1H,t,J=2.8Hz), 5.06(1H,s),
5.20(1H,d,J=7.3Hz), 5.33(2H,br), 6.03(1H,d,J=4.4Hz),
6.09(1H,t,J=8.2Hz), 6.33(1H,d,J=2.8Hz), 6.36(1H,d,J=2.4Hz),
7.39(1H,s), 7.48(2H,t,J=7.8Hz), 7.61(1H,t,J=6.8Hz),
8.12(2H,d,J=7.4Hz).
FAB mass：952(MH+).
【０４２９】
実施例１０８
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-チエニル) プロピオニル]-4-Ｏ- エトキシカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０４３０】
融点；126-130 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.30-1.45(3H,m), 1.41(3H,s), 1.61(3H,s), 1.64(3H,s),
1.67(3H,s), 1.84(1H,s), 2.00-2.12(1H,m), 2.17-2.30(2H,m),
2.45(1H,dd,J=15.1Hz,J=9.8Hz), 2.52-2.94(7H,m),
3.73(4H,t like,J-4.4Hz), 3.79(1H,d,J=7.3Hz), 4.06(1H,br),
4.13-4.46(3H,m), 4.46-4.70(3H,m), 5.03(1H,t,J=3.9Hz),
5.16-5.27(2H,m), 5.53(2H,br), 5.86-6.02(1H,m), 6.10(1H,d,J=4.4Hz),
6.97(1H,dd,J=4.9Hz,J=3.4Hz), 7.11(1H,d,J=3.4Hz), 7.18-7.35(1H,m),
7.44(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.04(2H,d,J=7.8Hz).
FAB mass：957(MH+).
【０４３１】
実施例１０９
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(2-チエニル) プロピオニル]-4-Ｏ- エトキシカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- ［2-(1- メチルピペラジン-4- イル) エチリデン] バッカチンIII
【０４３２】
融点；132-135 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.20-1.50(3H,s), 1.24(3H,s), 1.40(9H,s), 1.60(3H,s), 1.64(3H,s),
1.67(3H,s), 1.84(1H,s), 2.00-2.10(1H,m), 2.10-2.95(11H,m),
2.31(3H,s), 3.79(1H,d,J=7.3Hz), 4.06(1H,s), 4.11-4.50(3H,m),
4.53(1H,d,J=8.8Hz), 4.63(1H,s), 5.01(1H,t,J=4.4Hz), 5.21(2H,s like),
5.52(2H,br), 5.84-6.02(1H,m), 6.09(1H,d,J=4.9Hz),
6.97(1H,dd,J=14.9Hz,J=3.9Hz), 7.10(1H,d,J=3.9Hz), 7.20-7.35(1H,m),
7.44(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.04(2H,d,J=7.8Hz).
FAB mass：970(MH+).
【０４３３】
実施例１１０
9 β-13-Ｏ-[(2R,3R)-3-( ベンゾイルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
【０４３４】
融点；151-153 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.04-1.30(2H,m), 1.25(3H,s), 1.30-1.55(2H,m), 1.59(3H,s),
1.64(3H,s), 1.67(3H,s), 1.70-1.86(1H,m), 1.97(1H,s),
2.03-2.32(3H,m), 2.41(1H,dd,J=15.1Hz,J=9.7Hz), 2.90(1H,d,J=4.8Hz),
3.85(1H,d,J=7.3Hz), 4.07(1H,br s), 4.27(1H,d,J=8.8Hz),
4.32(1H,d,J=8.8Hz), 4.42(1H,br), 4.57(1H,br d,J=7.3Hz),
4.79(1H,d,J=2.9Hz), 5.06(1H,s), 5.19(1H,d,J=6.3Hz),
5.23(1H,d,J=7.3Hz), 5.44(1H,d,J=10.7Hz), 5.55(1H,d,J=17.6Hz),
5.89-6.18(4H,m), 6.36(1H,dd,J=3.4Hz,J=2.0Hz), 6.39(1H,d,J=3.4Hz).
FAB mass：868(MH+).
【０４３５】
実施例１１１
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-[2-(1- メチルピペラジン-4- イル) エチリデン] バッカチン III
【０４３６】
融点；124-127 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3-CD3OD(4:1(v/v))/TMS) δ(ppm):
1.10(4H,m), 1.28(3H,s), 1.41(9H,s), 1.57(3H,s), 1.63(3H,s),
1.74(3H,s), 2.04-3.20(16H,m), 2.70(3H,s), 3.84(1H,d,J=7.8Hz),
4.04(1H,br), 4.39(2H,AB type q,J=7.8Hz), 4.72(1H,br),
5.00(1H,t,J=3.6Hz), 5.05(1H,s), 5.23(1H,d,J=6.8Hz),
5.38(1H,d,J=6.8Hz), 6.03(2H,m), 6.33(1H,d,J=2.8Hz),
6.35(1H,t,J=2.0Hz), 7.37(1H,s), 7.48(2H,t,J=7.8Hz),
7.61(1H,t,J=7.3Hz), 8.05(2H,d,J=7.3Hz).
FAB mass：951(MH2 +).
【０４３７】
実施例１１２
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-ジメチルアミノエチリデン)バッカチン III
【０４３８】
融点；129-136 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm):
1.10(4H,m), 1.28(3H,s), 1.42(9H,s), 1.58(3H,s), 1.63(3H,s),
1.75(3H,s), 2.03-2.36(5H,m), 2.71(3H,s), 2.91(3H,s),
3.12(2H,m), 3.90(1H,d,J=6.8Hz), 4.05(1H,m),
4.30(2H,AB type q,J=8.8Hz), 4.72(1H,s), 5.06(1H,s), 5.21(1H,br),
5.30(1H,d,J=6.8Hz), 5.38(2H,m), 6.03(2H,m),
6.33(1H,d,J=2.8Hz), 6.35(1H,d,J=2.0Hz), 7.37(1H,s),
7.49(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz), 8.04(2H,d,J=7.8Hz).
FAB mass：896(MH2 +).
【０４３９】
実施例１１３
9 β-13-Ｏ-[(2R,3R)-3-( ベンゾイルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０４４０】
融点；148-151 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.04-1.30(2H,m), 1.25(3H,s), 1.34-1.53(2H,m), 1.58(3H,s),
1.62(3H,s), 1.63(3H,s), 1.72-1.84(1H,m), 1.93(1H,s),
2.00-2.24(3H,m), 2.40(1H,dd,J=15.1Hz,J=9.8Hz), 2.52-2.70(4H,m),
2.73(1H,dd,J=13.2Hz,J=4.9Hz), 2.81(1H,dd,J=13.2Hz,J=3.9Hz),
3.66-3.83(4H,m), 3.77(1H,d,J=6.8Hz), 4.05-4.08(1H,m),
4.27(1H,d,J=8.8Hz), 4.33(1H,d,J=8.8Hz9, 4.66(1H,d,J=8.3Hz),
4.79(1H,s like), 5.00(1H,t,J=3.9Hz), 5.06(1H,s), 5.17(1H,d,J=6.8Hz),
5.93(1H,dd,J=9.3Hz,J=2.5Hz), 6.02-6.15(2H,m), 6.35(1H,d,J=1.9Hz),
6.36(1H,dd,J=3.4Hz,J=1.9Hz), 7.12(1H,d,J=9.3Hz), 7.37(1H,s like),
7.40-7.59(5H,m), 7.61(1H,t,J=7.8Hz), 7.80(2H,d,J=8.3Hz),
8.04(2H,d,J=8.3Hz).
FAB mass：941(MH+).
【０４４１】
実施例１１４
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-7- デオキシ-4- Ｏ- エトキシカルボニル-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチンIII
【０４４２】
融点：118-119 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.37(3H,t,J=5.8Hz), 1.41(9H,s), 1.49(3H,s),
1.50-2.10(4H,m), 1.60(3H,s), 1.77(3H,s), 1.85(1H,s),
2.20(1H,dd,J=15.3Hz,J=3.4Hz), 2.45(1H,dd,J=15.3Hz,J=9.3Hz),
2.52-2.94(7H,m), 3.74(4H,t,J=4.4Hz), 4.02(1H,br),
4.11(1H,d,J=7.3Hz), 4.22(1H,d,J=8.8Hz), 4.25-4.57(3H,m), 4.71(1H,s),
5.00(1H,s), 5.05(1H,t,J=3.9Hz), 5.26(1H,d,J=7.3Hz),
5.35(1H,d,J=10.2Hz), 5.41(1H,d,J=10.2Hz), 5.97(1H,t,J=7.3Hz),
6.04(1H,d,J=4.4Hz), 6.25-6.40(2H,m), 7.38(1H,s), 7.44(2H,t,J=7.8Hz),
7.59(1H,t,J=7.8Hz), 8.07(2H,d,J=7.8Hz).
FAB mass；925(MH+)
【０４４３】
実施例１１５
9 β-13-Ｏ-[(2R,3R)-3-(tert- ブトキシカルボニルアミノ）-3-(2-フリル)-2-ヒドロキシプロピオニル]-4,10- ジデアセチル-7- デオキシ-4- Ｏ- エトキシカルボニル-9- ジヒドロ-9,10-Ｏ-(2-ジメチルアミノエチリデン) バッカチンIII
【０４４４】
融点：114-115 ℃（ジオキサンより凍結乾燥）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.36(3H,t,J=6.9Hz), 1.41(9H,s), 1.49(3H,s),
1.50-2.30(6H,m), 1.61(3H,s), 1.78(3H,s), 2.35-2.51(1H,m),
2.39(6H,m), 2.67(1H,dd,J=13.2Hz,J=5.4Hz),
2.76(1H,dd,J=13.2Hz,J=3.9Hz), 2.85(1H,d,J=4.9Hz),
4.11(1H,d,J=7.3Hz), 4.22(1H,d,J=8.8Hz), 4.23-4.57(3H,m), 4.71(1H,s),
4.95-5.08(2H,m), 5.27(1H,d,J=7.3Hz), 5.35(1H,d,J=8.8Hz),
5.42(1H,d,J=8.8Hz), 5.98(1H,t,J=7.8Hz), 6.04(1H,d,J=4.9H),
6.23-6.39(2H,m), 7.38(1H,s), 7.44(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.07(2H,d,J=7.8Hz).
FAB mass；883(MH+)
【０４４５】
【化３９】
【表６】
実施例１１６
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-7- デオキシ-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
【０４４８】
融点：148-151 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.40(9H,br s), 1.52(3H,s), 1.58(3H,s), 1.59(3H,s),
1.84(1H,s), 2.14(1H,dd,J=7.8,J=15.1Hz), 2.33(3H,s),
2.44(1H,dd,J=9.9,J=15.1Hz), 3.08(1H,d,J=5.9Hz), 3.97(1H,d,J=7.3Hz),
4.07-4.16(1H,br s), 4.24(1H,d,J=8.1Hz), 4.34(1H,d,J=8.1Hz),
4.63(1H,br s), 4.86(1H,br d,J=4.2Hz), 5.22(1H,d,J=7.3Hz),
5.26(1H,d,J=6.4Hz), 5.30(1H,br d,J=8.8Hz), 5.49(1H,d,J=10.7Hz),
5.61(1H,d,J=17.1Hz), 5.52-5.63(1H,m), 5.70(1H,dd,J=10.3,J=4.2Hz),
5.97-6.10(3H,m), 6.11(1H,d,J=10.3Hz), 7.25-7.43(5H,m),
7.48(2H,t,J=7.5Hz), 7.61(1H,t,J=7.5Hz), 8.13(2H,d,J=7.5Hz)
FAB mass : 830(MH+)
【０４４９】
実施例１１７
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-7- デオキシ-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
【０４５０】
融点：150-153 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.23(3H,s), 1.39(9H,s), 1.51(3H,s), 1.57(3H,s), 1.64(3H,br s),
1.84(1H,s), 2.15(1H,dd,J=7.3,J=14.8Hz), 2.32(3H,s),
2.39(1H,dd,J=9.5,J=14.8Hz), 2.55-2.70(4H,m),
2.75(1H,dd,J=4.9,J=13.7Hz), 2.82(1H,dd,J=3.9,J=13.7Hz),
3.07(1H,d,J=5.9Hz), 3.74(4H,t,J=4.6Hz), 3.91(1H,d,J=7.6Hz),
4.00-4.15(1H,br s), 4.24(1H,d,J=7.8Hz), 4.34(1H,d,J=7.8Hz),
4.63(1H,br s), 4.85(1H,d,J=4.2Hz), 5.05(1H,dd,J=3.9,J=4.9Hz),
5.15(1H,d,J=7.6Hz), 5.30(1H,br d,J=9.3Hz), 5.62(1H,br d,J=9.3Hz),
5.69(1H,dd,J=10.3,J=4.2Hz), 5.96(1H,d,J=5.9Hz),
6.03-6.09(1H,m), 6.07(1H,d,J=10.3Hz), 7.30-7.43(5H,m),
7.49(2H,t,J=7.3Hz), 7.61(1H,t,J=7.3Hz), 8.13(2H,d,J=7.3Hz)
【０４５１】
実施例１１８
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3-(4-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０４５２】
融点：162-165 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.22(3H,s), 1.41(9H,s), 1.42(3H,s), 1.52(3H,s), 1.53(3H,s),
1.57(3H,s), 1.60(3H,s), 1.86(1H,s), 2.34(3H,s), 2.05-2.17(1H,m),
2.32-2.43(1H,m), 3.07(1H,d,J=5.7Hz), 3.97(1H,d,J=7.3Hz),
4.22(1H,d,J=7.8Hz), 4.37(1H,d,J=7.8Hz), 4.39(1H,br s),
4.63(1H,br s), 4.86(1H,d,J=4.0Hz), 5.32(1H,br d,J=9.6Hz),
5.47(1H,d,J=7.3Hz), 5.69(1H,dd,J=4.0,J=10.3Hz), 5.73(1H,br d,J=9.6Hz),
5.98(1H,d,J=5.7Hz), 6.10(1H,d,J=10.3Hz), 6.02-6.14(1H,br),
7.36(2H,d,J=5.9Hz), 7.48(2H,t,J=7.4Hz), 7.61(1H,t,J=7.4Hz),
8.14(2H,d,J=7.4Hz), 8.60(2H,d,J=5.9Hz)
FAB mass : 833(MH+)
【０４５３】
実施例１１９
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-7-デオキシ-4,10-ジデアセチル-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチン III
【０４５４】
融点：127-130 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.23-1.29(3H,m), 1.41(9H,s), 1.53(3H,s), 1.60(6H,s), 1.70(3H,s),
1.77-1.92(2H,m), 2.27(1H,dd,J=8.3,J=15.3Hz),
2.39(1H,dd,J=9.5,J=15.3Hz), 2.44-2.70(2H,m), 3.12(1H,d,J=5.9Hz),
3.76(1H,br s), 4.01(1H,d,J=7.3Hz), 4.27(1H,d,J=8.3Hz),
4.34(1H,d,J=8.3Hz), 4.71(1H,br d,J=3.9Hz), 4.81(1H,d,J=4.2Hz),
5.22(1H,d,J=7.3Hz), 5.25(1H,d,J=6.4Hz), 5.33(2H,br s),
5.48(1H,d,J=10.7Hz), 5.60(1H,d,J=17.1Hz),
5.70(1H,dd,J=10.3,J=4.2Hz), 5.99(1H,d,J=5.9Hz),
6.00-6.13(2H,m), 6.12(1H,d,J=10.3Hz), 6.34(1H,d,J=2.9Hz),
6.35-6.38(1H,m), 7.40(1H,br s), 7.49(2H,t,J=7.3Hz),
7.62(1H,t,J=7.3Hz), 8.16(2H,d,J=7.3Hz)
【０４５５】
実施例１２０
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-7-デオキシ-4,10-ジデアセチル-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
【０４５６】
融点：132-135 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.01(3H,t,J=7.3Hz), 1.25(3H,s), 1.40(9H,s), 1.52(3H,s), 1.56(3H,s),
1.68(3H,s), 1.78-1.90(2H,m), 2.28(1H,dd,J=8.3,J=14.9Hz),
2.39(1H,dd,J=9.5,J=14.9Hz), 2.44-2.55(1H,m), 2.55-2.70(5H,m),
2.76(1H,dd,J=13.7,J=5.1Hz), 2.81(1H,dd,J=13.7,J=3.9Hz),
3.10(1H,d,J=6.2Hz), 3.75(4H,t,J=4.7Hz), 3.97(1H,d,J=7.5Hz),
4.26(1H,d,J=8.3Hz), 4.33(1H,d,J=8.3Hz), 4.71(1H,br s),
4.81(1H,d,J=3.9Hz), 5.04(1H,dd,J=5.1,J=3.9Hz), 5.16(1H,d,J=7.5Hz),
5.32(2H,br s), 5.70(1H,dd,J=10.3,J=3.9Hz), 5.96(1H,d,J=6.2Hz),
6.03-6.13(1H,m), 6.09(1H,d,J=10.3Hz), 6.30-6.40(2H,m), 7.40(1H,s),
7.50(2H,t,J=7.3Hz), 7.62(1H,t,J=7.3Hz), 8.16(2H,d,J=7.3Hz)
【０４５７】
実施例１２１
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル]-4-Ｏ- シクロプロパンカルボニル-7- デオキシ-4,10-ジデアセチル-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０４５８】
融点：165-168 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.25(s), 1.38(s), 1.42(s), 1.51(s), 1.57(s), 1.59(s), 2.20(1H,m),
2.28(1H,m), 3.11(1H,d,J=5Hz), 3.94(1H,d,J=7.5Hz), 4.14(1H,d,J=8Hz),
4.33(1H,d,J=8Hz), 4.54(1H,br), 4.75(1H,d,J=4Hz), 5.00(1H,d,J=9.5Hz),
5.45(1H,d,J=7.5Hz), 5.67(1H,dd,J=10Hz,J=4Hz), 5.85(1H,d,J=9.5Hz),
6.00(1H,d,J=5Hz), 6.07(1H,d,J=10Hz), 6.18(1H,t-br),
7.34(2H,d,J=5.5Hz), 7.50(2H,t,J=7.5Hz), 7.62(1H,t,J=7.5Hz),
8.07(2H,d,J=7.5Hz), 8.57(2H,d,J=5.5Hz).
FAB mass：873(M+).
【０４５９】
実施例１２２
9 β-13-Ｏ-[3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-2- メチル-3-(4-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０４６０】
融点：161-164 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.27(s), 1.34(9H,s), 1.42(s), 1.54(s), 1.58(s), 1.59(s), 2.22(2H,m),
2.52(3H,s), 3.10(1H,d,J=5.5Hz), 3.98(1H,d,J=7.5Hz),
4.24(1H,d,J=8Hz), 4.38(1H,d,J=8Hz), 4.85(1H,d,J=4Hz),
5.02(1H,d,J=10Hz), 5.44(1H,d,J=7.5Hz), 5.69(1H,dd,J=10Hz,J=4Hz),
5.74(1H,d,J=10Hz), 5.96(1H,d,J=5.5Hz), 6.10(1H,d,J=10Hz),
6.23(1H,t,J=9Hz), 7.35(2H,d,J=5Hz), 7.49(2H,t,J=7.5Hz),
7.61(1H,t,J=7.5Hz), 8.15(2H,d,J=7.5Hz), 8.60(2H,d,J=5Hz).
FAB mass：847(M+).
【０４６１】
実施例１２３
9 β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-4-Ｏ- シクロプロパンカルボニル-7- デオキシ-4,10-ジデアセチル-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ-(2-モルホリノエチリデン) バッカチン III
【０４６２】
融点：105-110 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.25(7H,s like), 1.41(9H,s), 1.50(3H,s), 1.56(3H,s), 1.71(3H,s),
2.33-2.44(3H,m), 2.64(4H,m), 2.79(2H,AB type q,J=8.3Hz),
3.10(1H,d,J=5.9Hz), 3.72-7.76(4H,m), 3.94(1H,d,J=7.3Hz),
4.25(2H,AB type q,J=8.3Hz), 4.73(1H,s), 4.78(1H,d,J=4.4Hz),
5.05(1H,dd,J=4.9Hz,J=3.9Hz), 5.45(1H,d,J=17.2Hz),
5.69(1H,dd,J=10.3Hz,J=3.9Hz), 5.98(1H,d,J=5.9Hz), 6.04(1H,m),
6.07(1H,d,J=10.7Hz), 6.32(1H,d,J=3.4Hz),
6.35(1H,dd,J=3.4Hz,J=2.0Hz), 7.36(1H,s), 7.50(2H,t,J=7.3Hz),
7.62(1H,t,J=7.3Hz), 8.10(2H,d,J=7.3Hz).
FAB mass：919(MH+).
【０４６３】
実施例１２４
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-(2-ピリジル) プロピオニル]-10- デアセチル-7- デオキシ-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
【０４６４】
融点：143-148 ℃（ジオキサンから凍結乾燥）
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.24(3H,s), 1.41(3H,s), 1.43(9H,s), 1.55(3H,s), 1.59(3H,s),
1.60(3H,s), 1.66(3H,s), 1.80(1H,s), 2.23-2.38(2H,m), 2.42(3H,s),
3.12(1H,d,J=5.9Hz), 4.06(1H,d,J=7.6Hz), 4.28(1H,d,J=8.3Hz),
4.33(1H,d,J=8.3Hz), 4.78(1H,br s), 4.87(1H,br s),
4.88(1H,d,J=4.2Hz), 5.35(1H,br d,J=9.8Hz), 5.47(1H,d,J=7.8Hz),
5.68(1H,dd,J=4.2,J=10.6Hz), 5.91(1H,d,J=9.8Hz), 5.94(1H,d,J=5.9Hz),
6.09(1H,d,J=10.6Hz), 6.05-6.15(1H,m), 7.20-7.28(1H,m),
7.41(1H,d,J=7.8Hz), 7.48(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz),
7.73(1H,d,J=7.8Hz), 8.14(2H,d,J=7.3Hz), 8.52(1H,d,J=4.4Hz)
【０４６５】
【化４０】
【表７】
実施例１２５
9 β-4- Ｏ- ブタノイル-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2- フリル)-2-ヒドロキシプロピオニル]-7-デオキシ-4,10-ジデアセチル-9- ジヒドロ-7β,8β- メチレン-9,10-Ｏ-(2-モルホリノエチリデン)-19- ノルバッカチン III
【０４６８】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
0.74(1H,br t,J=5.0Hz), 0.99(3H,t,J=7.6Hz), 1.18-1.80(9H,m),
1.20(3H,s), 1.35(9H,s), 1.53(3H,s), 2.29(1H,dd,J=8.8,J=15.6Hz),
2.40-2.77(10H.m), 3.12(1H,d,J=8.3Hz), 3.36(1H,br s),
3.72(4H,t,J=4.6Hz), 4.13(1H,dd,J=7.8,J=2.6Hz), 4.32(1H,d,J=7.8Hz),
4.47-4.55(2H,m), 4.67(1H,br s), 4.91(1H,t,J=4.4Hz),
5.09(1H,d,J=7.3Hz), 5.24(1H,d,J=9.7Hz), 5.38(1H,br d,J=9.7Hz),
5.52(1H,d,J=8.3Hz), 6.22(1H,br t,J=8.8Hz), 6.35(1H,d,J=2.9Hz),
6.39(1H,dd,J=2.9,J=1.5Hz), 7.42(1H,d,J=1.5Hz), 7.49(2H,t,J=7.8Hz),
7.57(1H,t,J=7.8Hz), 8.08(2H,d,J=7.8Hz)
【０４６９】
実施例１２６
9 β-13-Ｏ-[(2R,3S)-3-(tert-ブトキシカルボニルアミノ)-2-ヒドロキシ-3- フェニルプロピオニル]-10- デアセチル-7- デオキシ-9- ジヒドロ-7β,8β- メチレン-9,10-Ｏ-(2-モルホリノエチリデン)-19- ノルバッカチン III
【０４７０】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
0.77(1H,br s), 1.10-1.80(3H,m), 1.21(3H,s), 1.34(9H,s), 1.54(3H,s),
1.68(3H,s), 1.75(1H,s), 2.23(3H,s), 2.31(1H,dd,J=8.8,J=15.6Hz),
2.50-2.78(8H.m), 3.12(1H,d,J=8.3Hz), 3.48(1H,br s),
3.72(4H,t,J=4.6Hz), 4.17(1H,dd,J=7.8,J=2.0Hz), 4.32-4.48(2H,m),
4.54(1H,t,J=8.8Hz), 4.60(1H,br s), 4.91(1H,t,J=4.2Hz),
5.09(1H,d,J=7.3Hz), 5.31(1H,br d,J=9.1Hz), 5.47(1H,d,J=9.1Hz),
5.53(1H,d,J=8.3Hz), 6.20(1H,br t,J=8.3Hz), 7.30-7.43(5H,m),
7.49(2H,t,J=7.8Hz), 7.57(1H,t,J=7.8Hz), 8.08(2H,d,J=7.8Hz)
【０４７１】
参考例１
【０４７２】
【化４１】
工程１：９β-10-デアセチル-13-デオキシ-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-13-オキソバッカチン III
実施例１の工程２で得た化合物 0.1301 g をジオキサン 6.5 ml に溶解させ、室温で二酸化マンガン 0.823 gを添加し、室温で15時間激しく撹拌した。反応液をセライト濾過し、濾過物をクロロホルムで洗浄し、濾液の溶媒を減圧留去した。得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：アセトン＝10:1(v/v) ）で精製し、標記化合物 0.1154 g を無色透明シロップ状の物質として得た。
【０４７４】
Rf=0.60 ( クロロホルム：アセトン＝10:1(v/v) ）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.27(3H,s), 1.43(3H,s), 1.61(3H,s), 1.66(3H,s), 1.68(3H,s),
1.94(3H,s), 2.01(1H,s), 2.17(2H,m), 2.22(3H,s),
2.64(1H,AB type d,J=20.0Hz), 2.90(1H,AB type d,J=20.0Hz),
3.15(1H,d,J=4.4Hz), 3.99(1H,d,J=7.3Hz), 4.07(1H,m),
4.24(1H,AB type d,J=7.8Hz), 4.65(1H,AB type d,J=7.8Hz),
4.41(1H,dd,J=1.5Hz,8.8Hz), 5.04(1H,s), 5.68(1H,d,J=7.3Hz),
6.16(1H,d,J=4.8Hz), 7.49(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.11(2H,d,J=7.8Hz).
【０４７５】
工程２：９β-10-デアセチル-13-デオキシ-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-13-オキソ-7−Ｏ−トリエチルシリルバッカチン III
上記工程１で得た化合物 73.0 mgを塩化メチレン 2.2 ml に溶解させ、-32 ℃で 2,6−ルチジン 0.075 ml およびトリエチルシリルトリフルオロメタンスルホナート 0.112 ml を添加した。30分後、-30 ℃で飽和重曹水を加え、クロロホルムで抽出し、飽和食塩水で洗浄して無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；クロロホルム：メタノール＝ 8.5:1(v/v) ）で精製し、標記化合物 48.3 mgを白色固体として得た。
【０４７６】
Rf=0.40 ( ヘキサン：酢酸エチル＝7:1(v/v))
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.60(6H,q,J=7.8Hz), 0.95(9H,t,J=7.8Hz), 1.24(3H,s), 1.44(3H,s),
1.54(3H,s), 1.61(3H,s), 1.67(3H,s), 1.94(3H,s), 2.21(3H,s),
1.98-2.13(2H,m), 2.62(1H,AB type d,J=20.0Hz),
2.93(1H,AB type d,J=20.0Hz), 3.23(1H,d,J=5.4Hz), 4.07(1H,t,J=2.9Hz),
4.21(1H,AB type d,J=7.8Hz), 4.43(1H,AB type d,J=7.8Hz),
4.30(1H,broad d), 4.78(1H,t,J=4.0Hz), 5.61(1H,d,J=7.8Hz),
6.07(1H,d,J=5.4Hz), 6.94(1H,d,J=7.8Hz), 7.49(2H,t,J=7.8Hz),
7.60(1H,t,J=7.8Hz), 8.12(2H,d,J=7.8Hz).
【０４７７】
工程３：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン−7-Ｏ−トリエチルシリルバッカチン III
上記工程２で得た化合物 48.3 mgをテトラヒドロフラン−メタノール（20:1(v/v) ）の混合溶媒に溶解させ、室温で水素化ホウ素ナトリウム 11.0 mgを添加した。1.5 時間後、0 ℃で飽和塩化アンモニウム水溶液を加えて中和し、酢酸エチルで抽出した。飽和食塩水で洗浄して無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分 48.3 mgを塩化メチレン 2.5 ml に溶解させ、-82 ℃で 1.0規定水素化ジイソブチルアルミニウム（トルエン溶液, 0.17 ml ）を滴下し、10分間撹拌した。-78 ℃でメタノールを注加し、ロシェル塩（0.23 g）の水溶液（水 1.5 ml ）を添加して室温で1 時間激しく撹拌した。クロロホルムで抽出し、飽和食塩水で洗浄して無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝2:1(v/v)）で精製し、標記化合物 10.8 mgを無色透明シロップ状の物質として得た。
【０４７８】
Rf=0.49 ( ヘキサン：酢酸エチル＝2:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.61(6H,q,J=7.8Hz), 0.95(9H,t,J=7.8Hz), 1.12(3H,s), 1.40(3H,s),
1.49(3H,s), 1.56(3H,s), 1.57(3H,s), 1.93(3H,s), 1.95-2.11(3H,m),
2.26-2.44(2H,m), 2.32(3H,s), 3.16(1H,d,J=4.9Hz), 4.06(1H,t,J=4.8Hz),
4.21(1H,AB type d,J=7.8Hz), 4.54(1H,AB type d,J=7.8Hz),
4.72-4.84(2H,m), 5.51(1H,d,J=7.8Hz), 5.91(1H,d,J=4.9Hz),
7.48(2H,t,J=7.3Hz), 7.59(1H,t,J=7.3Hz), 8.13(2H,d,J=7.3Hz).
【０４７９】
工程４：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-( トリイソプロピルシリルオキシ) プロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ−トリエチルシリルバッカチン III
上記工程３で得た化合物と (3R,4R)-1-(tert−ブトキシカルボニル)-4-(2−フリル)-3-( トリイソプロピルシリルオキシ) アゼチジン-2−オンを実施例１の工程３と同様に反応させ、精製して、標記化合物を得た。
【０４８０】
Rf=0.25 ( ヘキサン：酢酸エチル＝6:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.62(6H,q,J=7.8Hz), 0.85-1.01(30H,m), 1.06(3H,s), 1.23(3H,s),
1.38(9H,s), 1.46(6H,s), 1.50(3H,s), 1.76(3H,s), 2.04-2.29(3H,m),
2.43(3H,s), 2.36-2.45(1H,m), 3.16(1H,d,J=5.4Hz),
3.98(1H,dd,J=8.4Hz,3.2Hz), 4.25(1H,d,J=8.0Hz), 4.40-4.48(1H,m),
4.50(1H,d,J=8.0Hz), 4.83(1H,t,J=6.8Hz), 4.96(1H,s), 5.25-5.36(2H,m),
5.41(1H,d,J=4.8Hz), 5.89(1H,d,J=5.4Hz), 6.12(1H,t),
6.24(1H,d,J=3.2Hz), 6.34(1H,d,J=3.2Hz), 7.36(1H,s),
7.48(2H,t,J=7.2Hz), 7.57(1H,t,J=7.2Hz), 8.11(2H,d,J=7.2Hz).
【０４８１】
工程５：９β-13-Ｏ-[(2R,3R)-3-(tert-ブトキシカルボニルアミノ)-3-(2−フリル)-2-ヒドロキシプロピオニル]-10−デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程３で得た化合物を実施例１の工程４と同様に反応させ、実施例１の工程４で得た化合物と同じ標記化合物を得た。
【０４８２】
参考例２
【０４８３】
【化４２】
９β-4−Ｏ−ブタノイル-4,10-ジデアセチル-13-デオキシ-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-13-オキソバッカチン III
参考例１の工程１で得た化合物 84.9 mgをテトラヒドロフラン 2.9 ml に溶解させ、-58 ℃で 1規定ナトリウムヘキサメチルジシラジド 0.73 ml（テトラヒドロフラン溶液）を滴下し、5 分後にヨウ化エチル 0.058 ml を添加した。1.5 時間後、-52 ℃で飽和塩化アンモニウム水溶液を注加し、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝5:2(v/v)）で精製し、標記化合物 19.1 mgを無色透明シロップ状の物質として得た。
【０４８５】
Rf=0.23 ( ヘキサン：酢酸エチル＝5:2(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.06(3H,t,J=7.3Hz), 1.26(3H,s), 1.43(3H,s), 1.61(3H,s), 1.67(3H,s),
1.68(3H,s), 1.68-1.80(2H,m), 1.93(3H,s), 1.97(1H,s),
2.12-2.23(2H,m), 2.38-2.54(2H,m), 2.62 (1H,AB type d,J=19.5Hz),
2.89(1H,AB type d,J=19.5Hz), 3.17(1H,d,J=4.4Hz), 3.99(1H,d,J=7.3Hz),
4.05-4.11(1H,m), 4.24(1H,AB type d,J=8.8Hz),
4.67(1H,AB type d,J=8.8Hz), 4.42(1H,dd,J=8.3Hz,0.9Hz), 5.00(1H,s),
5.67(1H,d,J=7.3Hz), 6.15(1H,d,J=4,4Hz), 7.49(2H,t,J=8.3Hz),
7.62(1H,t,J=8.3Hz), 8.11(2H,d,J=8.3Hz).
【０４８６】
参考例３
【０４８７】
【化４３】
９β-4−Ｏ−ブタノイル-4,10-ジデアセチル-13-デオキシ-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-13-オキソ-7−Ｏ−トリエチルシリルバッカチン III
参考例１の工程２で得た化合物を原料に用い、参考例２と同様の操作を行うことにより、標記化合物を無色透明シロップ状の物質として得た。
【０４８９】
Rf=0.33 ( ヘキサン：酢酸エチル＝4:1(v/v)）
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.60(6H,q,J=8.0Hz), 0.94(9H,t,J=8.0Hz), 1.05(3H,t,J=7.6Hz),
1.22(3H,s), 1.43(3H,s), 1.53(3H,s), 1.61(3H,s), 1.65(3H,s),
1.66-1.82(2H,m), 1.93(3H,s), 1.98-2.13(2H,m), 2.32-2.53(2H,m),
2.59(1H,AB type d,J=19.5Hz), 2.91(1H,AB type d,J=19.5Hz),
3.22(1H,d,J=4.8Hz), 4.08(1H,t,J=4.0Hz), 4.21(1H,AB type d,J=7.7Hz),
4.44(1H,AB total d,J=7.7Hz), 4.24-4.35(1H,m), 4.74(1H,t,J=4.0Hz),
5.61(1H,d,J=7.5Hz), 6.07(1H,d,J=4.8Hz), 7.48(2H,t,J=7.7Hz),
7.61(1H,t,J=7.7Hz), 8.13(2H,d,J=7.7Hz).
FAB mass : 838(MH+).
【０４９０】
参考例４
【０４９１】
【化４４】
工程１：13−Ｏ−ベンジルオキシカルボニル-10-デアセチル-7,10-ビス−Ｏ-(2,2,2-トリクロロエトキシカルボニル) バッカチン III
2.409 g の 10-デアセチル-7,10-ビス−Ｏ-(2,2,2-トリクロロエトキシカルボニル) バッカチン IIIを 15 mlの乾燥したテトラヒドロフランに溶解し、-50 ℃に冷却下、0.92 gのベンジルオキシカルボニルクロリドを加え、続いて 5.38 mlの１規定ナトリウムヘキサメチルジシラジド（テトラヒドロフラン溶液）を滴下し、そのままの温度で 3時間撹拌した。反応液に塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥し、溶媒を減圧留去した。得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；10%(v/v)の酢酸エチルを含むヘキサン、途中から 15 ％に変更し、 さらに 20 ％に変更した）にて精製して、標記化合物 1.607 gを無色のガラス状の固体として得た。
【０４９３】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.18(3H,s), 1.19(3H,s), 1.84(3H,s), 2.0-2.2(1H,m), 2.06(1H,d,J=1Hz),
2.28(3H,s), 2.35(2H,m), 2.62(1H,ddd,J=15Hz,9Hz,7Hz),
3.94(1H,d,J=7Hz), 4.13(1H,d,J=8Hz), 4.32(1H,d,J=8Hz),
4.60(1H,d,J=12Hz), 4.76(1H,AB type d,J=12Hz),
4.79(1H,AB type d,J=12Hz), 4.91(1H,d,J=12Hz), 4.96(1H,d,J=8Hz),
5.25(2H,s), 5.60(1H,dd,J=11Hz,7Hz), 5.66(1H,d,J=7Hz),
5.95(1H,t,J=8Hz), 6.26(1H,s), 7.40(5H,s), 7.48(2H,t,J=7.5Hz),
7.62(1H,t,J=7.5Hz), 8.07(2H,m).
【０４９４】
工程２：13−Ｏ−ベンジルオキシカルボニル-10-デアセチルバッカチン III
上記工程１で得た化合物を実施例９の工程３と同様に反応させ、標記化合物を得た。
【０４９５】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.11(3H,s), 1.16(3H,s), 1.74(3H,s), 1.82(1H,m), 1.97(3H,s),
2.25(3H,s), 2.32(2H,m), 2.59(1H,ddd,J=14Hz,9.5Hz,6.5Hz),
3.96(1H,d,J=7Hz), 4.16(2H,m), 4.30(2H,m), 4.95(1H,d,J=8Hz),
5.24(3H,m), 5.65(1H,d,J=7Hz), 5.92(1H,t,J=8Hz), 7.40(5H,s),
7.48(2H,t,J=7.5Hz), 7.62(1H,t,J=7.5Hz), 8.07(2H,m).
【０４９６】
工程３：９β-13-Ｏ−ベンジルオキシカルボニル-10-デアセチル-9−ジヒドロバッカチン III
上記工程２で得た化合物 119 mg を 10 mlの乾燥した塩化メチレンに溶解し、室温にて 180 mg のテトラブチルアンモニウムボロヒドリドを加え、室温にて 15 時間撹拌した。反応液に１規定塩酸を加えて泡が出なくなるまで撹拌した。有機層をとり飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をメタノールに溶解し、３時間放置した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；6%(v/v) のメタノールを含むクロロホルム）で精製して、標記化合物 86 mgを白色粉末として得た。
【０４９７】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.25(3H,s), 1.64(3H,s), 1.75(3H,s), 1.80(3H,s), 1.91(1H,m),
2.19(3H,s), 2.29(2H,m), 2.49(1H,m), 3.08(1H,d,J=5Hz), 4.11(1H,br),
4.16(1H,d,J=8Hz), 4.34(2H,m), 4.98(1H,d,J=7Hz),
5.17(2H,d and br,J=12Hz), 5.27(1H,d,J=12Hz), 5.96(1H,t,J=8Hz),
6.09(1H,d,J=5Hz), 7.39(5H,m), 7.46(2H,t,J=7.5Hz),
7.58(1H,t,J=7.5Hz), 8.08(2H,d,J=7.5Hz).
【０４９８】
工程４：９β-13-Ｏ−ベンジルオキシカルボニル-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデンバッカチン III
上記工程３で得た化合物を実施例１の工程２と同様に反応させ、標記化合物をガラス状の固体として得た。
【０４９９】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.23(3H,s), 1.40(3H,s), 1.57(3H,s), 1.63(3H,s), 1.65(3H,s),
1.79(3H,s), 2.18(2H,m), 2.23(3H,s), 2.30(2H,m), 2.97(1H,d,J=5Hz),
3.89(1H,d,J=7.5Hz), 4.03(1H,m), 4.26(1H,d,J=8Hz), 4.38(1H,d,J=8Hz),
4.66(1H,d,J=8Hz), 5.09(1H,br), 5.18(1H,d,J=12Hz), 5.26(1H,d,J=12Hz),
5.55(1H,d,J=7.5Hz), 5.92(1H,t,J=8Hz), 5.99(1H,d,J=5Hz), 7.39(5H,m),
7.46(2H,t,J=7.5Hz), 7.59(1H,t,J=7.5Hz), 8.09(2H,d,J=7.5Hz).
【０５００】
工程５：９β-13-Ｏ−ベンジルオキシカルボニル-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ−トリエチルシリルバッカチン III
上記工程３で得た化合物を実施例３の工程２と同様に反応させ、標記化合物をガラス状の固体として得た。
【０５０１】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.62(6H,q,J=8Hz), 0.97(9H,t,J=7Hz), 1.15(3H,s), 1.38(3H,s),
1.47(3H,s), 1.51(3H,s), 1.79(3H,d,J=1Hz), 2.08(1H,m), 2.24(3H,s),
2.28-2.39(3H,m), 3.21(1H,d,J=6Hz), 3.94(1H,dd,J=10Hz,4Hz),
4.27(1H,d,J=8Hz), 4.46(1H,d,J=8Hz), 4.54(1H,br), 4.80(1H,t,J=7Hz),
5.19(1H,d,J=12Hz), 5.25(1H,d,J=12Hz), 5.42(1H,d,J=9Hz),
5.84(1H,d,J=6Hz), 5.88(1H,t,J=10Hz), 7.39(5H,m), 7.46(2H,t,J=7.5Hz),
7.59(1H,t,J=7.5Hz), 8.08(2H,d,J=7.5Hz).
【０５０２】
工程６：９β-10-デアセチル-9−ジヒドロ-9,10-Ｏ−イソプロピリデン-7−Ｏ−トリエチルシリルバッカチン III
上記工程５で得た化合物 122 mg を 10 mlエタノールに溶解し、40 mg の 10%パラジウム炭素を加え、水素雰囲気下で１時間撹拌した。不溶物を濾過にて除き、濾液の溶媒を減圧留去した。得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；5%(v/v) のアセトンを含むクロロホルム）で精製して、実施例３の工程３で得た化合物と同じ標記化合物 80 mgを得た。
【０５０３】
参考例５
【０５０４】
【化４５】
9 β-10-デアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-7-Ｏ- トリエチルシリルバッカチンIII
9 β-10-デアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII 0.4030 g を塩化メチレン 80 ml に溶解させ、室温で 2,6- ジ-tert-ブチルピリジン 0.232 ml を添加し、-78 ℃に冷却してから、トリエチルシリルトリフルオロメタンスルホネート 0.202 ml を滴下した。16分後、-78 ℃でメタノールと飽和炭酸水素ナトリウム水溶液を加え、 クロロホルムで抽出し、飽和食塩水で洗浄した。無水硫酸ナトリウムにて乾燥後、溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝20:1(v/v) →クロロホルム：アセトン＝7:1(v/v)）で精製し、標記化合物 0.4126 g を白色フォーム状の物質として得た。
【０５０６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.58-0.71(6H,m), 0.98(9H,t,J=7.8Hz), 1.09(3H,s), 1.56(3H,s),
1.60(3H,s), 1.75(1H,s), 1.94(3H,s), 2.00-2.45(4H,m), 2.30(3H,s),
3.19(1H,d,J=5.3Hz), 3.95(1H,dd,J=8.8Hz,J=5.8Hz), 4.32(1H,d,J=8.3Hz),
4.35(1H,d,J=8.3Hz), 4.61(1H,d,J=7.8Hz), 4.72-4.89(2H,m),
5.09(1H,d,J=5.8Hz), 5.33(1H,d,J=7.8Hz), 5.46(1H,d,J=10.7Hz),
5.56(1H,d,J=17.1Hz), 5.90(1H,d,J=5.3Hz),
6.16(1H,ddd,J=17.1Hz,J=10.7Hz,J=5.8Hz), 7.47(2H,t,J=7.3Hz),
7.59(1H,t,J=7.3Hz), 8.11(2H,d,J=7.3Hz).
【０５０７】
参考例６
【０５０８】
【化４６】
9 β-10-デアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-7- Ｏ- トリエチルシリルバッカチンIII
9 β-10-デアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチンIII を原料に用い、参考例５の工程１と同様の反応操作を行うことにより、標記化合物を得た。
【０５１０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.61(6H,q,J=7.8Hz), 0.96(9H,t,J=7.8Hz), 1.11(3H,s), 1.40(3H,s),
1.50(3H,s), 1.57(3H,s), 1.59(3H,s), 1.93(3H,s), 1.88-2.15(2H,m),
2.23-2.47(2H,m), 2.32(3H,s), 3.16(1H,d,J=5.3Hz), 4.17(1H,t,J=4.8Hz),
4.17-4.29(1H,m), 4.20(1H,d,J=7.8Hz), 4.54(1H,d,J=7.8Hz),
4.73-4.88(2H,m), 5.51(1H,d,J=7.8Hz), 5.91(1H,d,J=5.3Hz),
7.48(2H,t,J=7.3Hz), 7.59(1H,t,J=7.3Hz), 8.14(2H,t,J=7.3Hz).
【０５１１】
参考例７
【０５１２】
【化４７】
工程１：9 β-10-デアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-7,13- ビス- Ｏ- トリエチルシリルバッカチンIII
参考例５の工程１で得た化合物 2.115 g を塩化メチレン 150 ml に溶解させ、室温で 2,6- ルチジン 0.528 ml を添加し、-58 ℃に冷却してからトリエチルシリルトリフルオロメタンスルホネート 0.88 mlを滴下した。40分後、-52 ℃で 2,6- ルチジン 0.176 ml 、およびトリエチルシリルトリフルオロメタンスルホネート 0.293 ml を追加した。-52 ℃でメタノール、飽和炭酸水素ナトリウム水溶液を加え、クロロホルムで抽出し、飽和食塩水で洗浄した。無水硫酸ナトリウムにて乾燥後、溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝6:1(v/v)）で精製し、標記化合物 1.7763 g を白色フォーム状物質として得た。
【０５１４】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.55-0.73(6H,m), 0.99(9H,t,J=7.8Hz), 1.01(9H,t,J=7.8Hz), 1.14(3H,s),
1.52(3H,s), 1.53(3H,s), 1.72(1H,s), 1.87(3H,s), 2.01-2.16(2H,m),
2.26(3H,s), 3.21(1H,d,J=5.9Hz), 3.92(1H,dd,J=10.7Hz,J=5.3Hz),
4.32(1H,d,J=8.3Hz), 4.39(1H,d,J=8.3Hz), 4.59(1H,d,J=9.3Hz),
4.83(1H,dd,J=8.7Hz,J=5.3Hz), 4.94(1H,t,J=7.3Hz), 5.05(1H,d,J=5.9Hz),
5.30(1H,d,J=9.3Hz), 5.44(1H,d,J=10.7Hz), 5.82(1H,d,J=5.9Hz),
6.12(1H,ddd,J=17.6Hz,J=10.7Hz,J=5.9Hz), 7.46(2H,t,J=7.3Hz),
7.57(1H,t,J ＝7.3Hz), 8.08(2H,d,J=7.3Hz).
【０５１５】
工程２：9 β-4- Ｏ- ブタノイル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-7,13- ビス- Ｏ- トリエチルシリルバッカチンIII
上記工程１で得た化合物 0.7671 g を乾燥したテトラヒドロフラン 37 mlに溶解させ、0 ℃でナトリウムビストリメチルシリルアミド（1.0 mol/L テトラヒドロフラン溶液） 4.7 ml を滴下し、15分後にヨウ化エチル 0.37 mlを添加し、その温度のまま30分撹拌した。0 ℃で飽和塩化アンモニウム水溶液を加え、酢酸エチルで希釈して分液し、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。減圧濃縮し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝7:1(v/v)）で精製し、標記化合物 0.2604 g を白色ガラス状物質として得た。
【０５１６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.58-0.73(12H,m), 0.93-1.10(21H,m), 1.15(3H,s), 1.52(3H,s),
1.53(3H,s), 1.70(1H,s), 1.74-1.90(2H,m), 1.85(3H,s),
2.01-2.12(2H,m), 2.17-2.30(1H,m), 2.32-2.43(1H,m), 2.45-2.63(2H,m),
3.19(1H,d,J=5.9Hz), 3.93(1H,dd,J=11.3Hz,J=5.4Hz),
4.32(1H,d,J=8.3Hz), 4.39(1H,d,J=8.3Hz), 4.58(1H,d,J=8.8Hz),
4.79(1H,dd,J=8.8Hz,J=4.9Hz), 4.94(1H,t,J=8.3Hz), 5.05(1H,d,J=5.9Hz),
5.29(1H,d,J=8.8Hz), 5.44(1H,d,J=10.8Hz), 5.55(1H,d,J=17.6Hz),
5.81(1H,d,J=5.9Hz), 6.11(1H,ddd,J=17.6Hz,J=10.8Hz,J=5.9Hz),
7.46(2H,t,J=7.8Hz), 7.58(1H,t,J=7.8Hz), 8.09(2H,d,J=7.8Hz).
【０５１７】
工程３：9 β-4- Ｏ- ブタノイル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
上記工程２で得た化合物 0.1414 g をピリジン 7.0 ml に溶解させ、0 ℃でフッ化水素ピリジン 1.41 mlを徐々に滴下した。滴下終了後、室温で14時間撹拌した。0 ℃で冷水を加え、酢酸エチルで希釈して分液し、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。減圧濃縮し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；クロロホルム：アセトン＝7:1(v/v)）で精製し、標記化合物 69.7 mgを白色ガラス状物質として得た。
【０５１８】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.06(3H,s), 1.16(3H,s), 1.62(3H,s), 1.65(3H,s), 1.73-1.86(2H,m),
1.90-2.00(1H,m), 1.93(3H,s), 2.10-2.29(3H,m),
2.34(1H,dd,J=15.6Hz,J=9.7Hz), 2.60(2H,t,J=7.8Hz),
3.05(1H,d,J=4.9Hz), 3.88(1H,d,J=6.8Hz), 4.06-4.18(1H,m),
4.33(1H,d,J=8.4Hz), 4.40(1H,dd,J=8.4Hz,J=1.5Hz), 4.59(1H,d,J=8.3Hz),
4.78(1H,br q,J=7.4Hz), 5.02(1H,s), 5.22(1H,d,J=5.9Hz),
5.30(1H,d,J=6.8Hz), 5.44(1H,d,J=10.8Hz), 5.56(1H,d,J=17.1Hz),
5.95-6.13(2H,m), 7.48(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.14(2H,d,J=7.8Hz).
【０５１９】
工程４：9 β-4- Ｏ- ブタノイル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-7-Ｏ- トリエチルシリルバッカチンIII
上記工程３で得た化合物を原料に用い、参考例５の工程１と同様の反応操作を行うことにより、標記化合物を得た。
【０５２０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.64(6H,q like,J=7.8Hz), 0.98(9H,t,J=7.8Hz), 1.05(3H,s), 1.41(3H,s),
1.56(3H,s), 1.61(3H,s), 1.71-1.84(2H,m), 1.76(1H,s), 1.94(3H,s),
1.95-2.63(7H,m), 3.18(1H,d,J=4.8Hz), 3.96(1H,dd,J=8.3Hz,J=5.8Hz),
4.32(1H,d,J=8.3Hz), 4.37(1H,d,J=8.3Hz), 4.58(1H,br d,J=7.8Hz),
4.70-4.81(2H,m), 5.10(1H,d,J=5.9Hz), 5.33(1H,d,J=8.4Hz),
5.46(1H,d,J=10.2Hz), 5.57(1H,d,J=17.6Hz), 5.90(1H,d,J=4.8Hz),
6.16(1H,ddd,J=17.6Hz,J=10.2Hz,J=5.9Hz), 7.47(2H,t,J=7.8Hz),
7.59(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz).
【０５２１】
参考例８
【０５２２】
【化４８】
工程１：9 β-4,10-ジデアセチル-9- ジヒドロ-4- Ｏ- プロパノイル-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
参考例７の工程１で得た化合物を原料に用い、ヨウ化エチルの代わりにヨウ化メチルを使用し、参考例７の工程２と同様の反応操作を実施した。次いで、参考例７の工程３と同様の反応操作を行うことにより、白色ガラス状の標記化合物を得た。
【０５２４】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.16(3H,s), 1.26(3H,t,J=7.4Hz), 1.62(3H,s), 1.65(3H,s),
1.82(1H,br s), 1.93(3H,s), 2.09-2.25(3H,m),
2.33(1H,dd,J=14.0Hz,J=10.0Hz), 2.66(2H,q,J=7.4Hz),
3.05(1H,d,J=4.9Hz), 3.89(1H,d,J=7.4Hz), 4.06-4.16(1H,br),
4.33(1H,d,J=8.8Hz), 4.39(1H,d,J=8.8Hz), 4.53-4.63(1H,br),
4.72-4.84(1H,br), 5.02(1H,s like), 5.22(1H,d,J=6.4Hz),
5.30(1H,d,J=7.4Hz), 5.45(1H,d,J=10.8Hz), 5.56(1H,d,J=17.6Hz),
5.96-6.10(2H,m), 7.47(2H,t,J=7.4Hz), 7.60(1H,t,J=7.4Hz),
8.13(2H,d,J=7.4Hz).
【０５２５】
工程２：9 β-4,10-ジデアセチル-9- ジヒドロ-4- Ｏ- プロパノイル-9,10-Ｏ-(2-プロペニリデン)-7-Ｏ- トリエチルシリルバッカチンIII
上記工程１で得た化合物を原料に用い、参考例５の工程１と同様の反応操作を行うことにより、白色ガラス状の標記化合物を得た。
【０５２６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.58-0.71(6H,m), 0.98(9H,t,J=7.8Hz), 1.09(3H,s), 1.25(3H,s),
1.56(3H,s), 1.60(3H,s), 1.75(1H,s), 1.94(3H,s), 1.98-2.16(2H,m),
2.23-2.44(2H,m), 2.62(2H,q,J=7.3Hz), 3.19(1H,d,J=5.4Hz),
3.96(1H,dd,J=8.8Hz,J=5.8Hz), 4.32(1H,d,J=8.3Hz), 4.37(1H,d,J=8.3Hz),
4.59(1H,d,J=8.7Hz), 4.71-4.82(2H,m), 5.09(1H,d,J=5.9Hz),
5.33(1H,d,J=8.7Hz), 5.46(1H,d,J=10.8Hz), 5.56(1H,d,J=17.6Hz),
5.90(1H,d,J=5.4Hz), 6.16(1H,ddd,J=17.6Hz,J=10.8Hz,J=5.9Hz),
7.46(2H,t,J=7.3Hz), 7.58(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz).
【０５２７】
参考例９
【０５２８】
【化４９】
工程１：9 β-10-デアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-7,13-ビス- Ｏ- トリエチルシリルバッカチンIII
参考例６の工程１で得た化合物を原料に用い、参考例７の工程１と同様の反応操作を実施することにより、標記化合物を得た。
【０５３０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.56-0.70(12H,m), 0.90-1.04(18H,m), 1.15(3H,s), 1.31(3H,s),
1.37(3H,s), 1.45(3H,s), 1.55(3H,s), 1.87(3H,s), 2.03-2.36(4H,m),
2.27(3H,s), 3.20(1H,d,J=5.8Hz), 3.94(1H,dd,J=9.2Hz,J=3.6Hz),
4.42(1H,d,J=8.0Hz), 4.50(1H,d,J=8.0Hz), 4.54(1H,d,J=9.2Hz),
4.83(1H,t,J=7.3Hz), 4.94(1H,dd,J=8.2Hz,J=7.8Hz), 5.41(1H,d,J=9.2Hz),
5.7(1H,d,J=5.8H), 7.44-7.84(2H,m), 7.56-7.59(1H,m), 8.07-8.09(2H,m).
【０５３１】
工程２：9 β-4- Ｏ- ブタノイル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-7,13-ビス- Ｏ- トリエチルシリルバッカチンIII
上記工程１で得られた化合物を原料に用い、参考例７の工程２と同様の反応操作を実施することにより、無色ガラス状固体の標記化合物を得た。
【０５３２】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.58-0.70(12H,m), 0.91-1.07(21H,m), 1.16(3H,s), 1.38(3H,s),
1.46(3H,s), 1.47(3H,s), 1.56(3H,s), 1.85(3H,s), 2.04-2.28(6H,m),
2.53(1H,dt,J=8.0Hz,J=6.0Hz), 2.54(1H,dt,J=8.0Hz,J=6.0Hz),
3.19(1H,d,J=5.9Hz), 3.97(1H,dd,J=9.9Hz,J=3.9Hz),
4.37(2H,AB type q,J=7.8Hz), 4.54(1H,d,J=9.3Hz), 4.80(1H,t,J=7.3Hz),
4.94(1H,t,J=7.8Hz), 5.41(1H,d,J=9.3Hz), 5.79(1H,d,J=5.9Hz),
7.46(2H,t,J=7.8Hz), 7.57(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
FAB mass：843(MH+)
【０５３３】
工程３：9 β-4- Ｏ- ブタノイル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチンIII
上記工程２で得た化合物を原料に用い、参考例７の工程３と同様の反応操作を実施することにより、無色ガラス状固体の標記化合物を得た。
【０５３４】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.07(3H,s), 1.16(3H,s), 1.42(3H,s), 1.58(3H,s), 1.63(3H,s),
1.64(3H,s), 1.84(3H,s), 1.93(3H,s), 1.97-2.40(4H,m),
2.59(2H,dd,J=7.8Hz,J=7.3Hz), 3.06(1H,d,J=4.9Hz), 3.85(1H,d,J=7.3Hz),
4.10(1H,s), 4.37(2H,AB type q,J=8.5Hz), 4.67(1H,d,J=7.8Hz),
4.79(1H,dd,J=8.5Hz,J=5.7Hz), 5.02(1H,br), 5.59(1H,d,J=7.3Hz),
6.03(1H,d,J=4.9Hz), 7.48(2H,t,J=7.8Hz), 7.60(1H,t,J=7.3Hz),
8.13(2H,d,J=7.3Hz).
【０５３５】
工程４：9 β-4- Ｏ- ブタノイル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-7- Ｏ- トリエチルシリルバッカチンIII
上記工程３で得た化合物を原料に用い、参考例５の工程１と同様の反応操作を実施することにより、無色ガラス状固体の標記化合物を得た。
【０５３６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.61(6H,q,J=7.8Hz), 0.95(9H,t,J=7.8Hz), 1.06(3H,t,J=7.3Hz),
1.13(3H,s), 1.41(3H,s), 1.51(3H,s), 1.57(3H,s), 1.59(3H,s),
1.77-1.83(2H,m), 1.94(3H,s), 2.27-2.39(4H,m), 2.59(2H,m),
3.65(1H,d,J=5.4Hz), 3.65(1H,dd,J=7.8Hz,J=4.4Hz),
4.18(2H,AB type q,J=7.8Hz), 4.56(1H,d,J=7.8Hz), 4.48-4.83(2H,m),
5.52(1H,d,J=7.8Hz), 5.93(1H,d,J=5.4Hz), 7.43(2H,t,J=7.8Hz),
7.59(1H,t,J=7.8Hz), 8.15(2H,d,J=7.8Hz).
【０５３７】
参考例１０
【０５３８】
【化５０】
工程１：9 β-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-4- Ｏ- プロパノイル-7,13-ビス- Ｏ- トリエチルシリルバッカチンIII
窒素雰囲気下、0 ℃でジイソプロピルアミン 1.17 mlを乾燥したテトラヒドロフラン 21 mlに溶解させ、n-ブチルリチウム (1.69 mol/L, ヘキサン溶液）を添加し、20分撹拌した。これを-78 ℃に冷却し、参考例９の工程１で得た化合物 728 mg を乾燥したテトラヒドロフラン 7 ml に溶解させたものを滴下した。1 時間後、-78 ℃でヨウ化メチル 1.11 mlを添加し、さらに4 時間撹拌しながら、徐々に-5℃まで昇温した。飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝10：1(v/v)）で精製し、無色ガラス状固体として標記化合物 706
mg を得た。
【０５４０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.61-0.72(12H,m), 0.91-1.02(18H,m), 1.16(3H,s), 1.25(3H,t,J=7.3Hz),
1.38(3H,s), 1.46(3H,s), 1.50(3H,s), 1.56(3H,s), 1.85(3H,s),
2.02-2.26(4H,m), 2.63(2H,q,J=7.3Hz), 3.19(1H,d,J=5.9Hz),
3.96(1H,dd,J=9.3Hz,J=3.4Hz), 4.30(2H,AB type q,J=7.8Hz),
4.54(1H,d,J=8.8Hz), 4.80(1H,t,J=7.3Hz), 4.95(1H,t,J=8.3Hz),
5.40(1H,d,J=9.3Hz), 5.78(1H,d,J=5.9Hz), 7.46(2H,t,J=7.3Hz),
7.58(1H,t,J=7.3Hz), 8.10(2H,d,J=7.3Hz).
FAB mass：829(MH+)
【０５４１】
工程２：9 β-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-4- Ｏ- プロパノイルバッカチンIII
上記工程１で得た化合物を原料に用い、参考例７の工程３と同様の反応操作を実施することにより、無色ガラス状固体の標記化合物を得た。
【０５４２】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.16(3H,s), 1.27(3H,t,J=7.3Hz), 1.42(3H,s), 1.50(3H,s), 1.63(3H,s),
1.64(3H,s), 1.94(3H,s), 2.11-2.36(4H,m), 2.66(2H,q,J=7.3Hz),
3.06(1H,d,J=4.9Hz), 3.85(1H,d,J=7.3Hz), 4.52(2H,AB type q,J=8.3Hz),
4.67(1H,d,J=8.3Hz), 4.79(1H,m), 5.02(1H,s), 5.59(1H,d,J=7.3Hz),
6.02(1H,d,J=4.9Hz), 7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.14(2H,d,J=7.8Hz).
【０５４３】
工程３：9 β-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-4- Ｏ- プロパノイル- ７- Ｏ- トリエチルシリルバッカチンIII
上記工程２で得た化合物を原料に用い、参考例５の工程１と同様の反応操作を実施することにより、無色ガラス状固体の標記化合物を得た。
【０５４４】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.57-0.64(6H,m), 0.93-0.98(9H,m), 1.12(3H,s), 1.26(3H,t,J=7.3Hz),
1.40(3H,s), 1.51(3H,s), 1.57(3H,s), 1.58(3H,s), 1.77(1H,s),
1.94(3H,s), 1.96-2.35(4H,m), 2.65(2H,q,J=7.3Hz), 3.16(1H,d,J=5.6Hz),
4.08(1H,t,J=4.9Hz), 4.20(2H,d,J=7.8Hz), 4.56(1H,d,J=7.8Hz),
4.74-4.78(2H,m), 5.20(1H,d,J=8.3Hz), 5.93(1H,d,J=5.4Hz),
7.46(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.15(2H,d,J=7.8Hz).
FAB mass：715(MH+)
【０５４５】
参考例１１
【０５４６】
【化５１】
工程１：9 β-10-デアセチル-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ-(2-プロペニリデン)-7,13- ビス- Ｏ- トリエチルシリルバッカチンIII
参考例７の工程１で得た化合物 1.0789 g を N,N- ジメチルホルムアミド 26.9 mlに溶解させ、室温でイミダゾール 0.595 gを添加し、0 ℃でジメチルクロロシラン 0.736 ml を滴下し、撹拌した。1 時間後、0 ℃で冷水を加え、ヘキサン- 酢酸エチル混合溶媒（1:1(v/v)）で抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝9:1(v/v)）で精製し、白色フォーム状の標記化合物 0.994 gを得た。
【０５４８】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.34(3H,d,J=2.9Hz), 0.03(3H,d,J=2.9Hz), 0.58-0.76(12H,m),
0.92-1.09(18H,m), 1.11(3H,s), 1.522(3H,s), 1.528(3H,s), 1.86(3H,s),
2.02-2.16(1H,m), 2.23-2.44(3H,m), 2.26(3H,s), 3.19(1H,d,J=5.3Hz),
3.88(1H,dd,J=10.7Hz,J=4.9Hz), 4.33(1H,d,J=7.8Hz),
4.41(1H,d,J=7.8Hz), 4.52-4.68(2H,m), 4.83(1H,dd,J=8.8Hz,J=5.4Hz),
4.98(1H,t,J=9.0Hz), 5.04(1H,d,J=6.4Hz), 5.27(1H,d,J=9.3Hz),
5.42(1H,d,J=10.7Hz), 5.53(1H,d,J=17.5Hz), 5.89(1H,d,J=5.3Hz),
6.11(1H,ddd,J=17.5Hz,J=10.7Hz,J=6.4Hz), 7.45(2H,t,J=7.8Hz),
7.56(1H,t,J=7.8Hz), 8.10(2H,d,J=7.8Hz).
【０５４９】
工程２：9 β-4,10-ジデアセチル-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ-(2-プロペニリデン)-7,13- ビス- Ｏ- トリエチルシリルバッカチンIII
上記工程１で得た化合物 0.994 gを乾燥したテトラヒドロフラン 50 mlに溶解させ、0 ℃でナトリウムビス(2- メトキシエトキシ) アルミニウムヒドリド 2.7 ml (65 %(w/v), トルエン溶液) を滴下し、0 ℃で50分撹拌した。0 ℃でジエチルエーテル 250 ml を加え、酒石酸カリウムナトリウム４水和物 12.8 g を水 70 mlに溶解させた水溶液を徐々に添加し、添加終了後に室温に戻し、1 時間激しく撹拌した。酢酸エチルで抽出し、飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝9:1(v/v)）で精製し、無色ガラス状の標記化合物 0.8413 g を得た。
【０５５０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.27(3H,d,J=2.4Hz), -0.01(3H,d,J=2.4Hz), 0.54-0.67(6H,m),
0.69-0.85(6H,m), 0.95(3H,t,J=7.8Hz), 0.97(3H,s), 1.05(9H,t,J=7.9Hz),
1.44(3H,s), 1.55(3H,s), 1.81(3H,s),
2.10(1H,ddd,J=13.6Hz,J=9.6Hz,J=4.2Hz),
2.20(1H,ddd,J=13.6Hz,J=8.2Hz,J=6.0Hz), 2,52(1H,dd,J=14.7Hz,J=9.8Hz),
2.87(1H,d,J=3.4Hz), 3.01(1H,dd,J=14.7Hz,J=1.4Hz),
3.62(1H,dd,J=9.6Hz,J=6.0Hz), 3.78(1H,s like), 4.28(1H,d,J=7.9Hz),
4.38-4.50(2H,m), 4.50-4.69(2H,m), 5.07(1H,d,J=6.4Hz),
5.33(1H,d,J=7.9Hz), 5.44(1H,d,J=10.2Hz), 5.55(1H,d,J=17.1Hz),
5.97(1H,d,J=3.5Hz), 6.20(1H,ddd,J=17.1Hz,J=10.2Hz,J=6.4Hz),
7.43(2H,t,J=7.4Hz), 7.53(1H,t,J=7.4Hz), 8.15(2H,d,J=7.4Hz).
【０５５１】
工程３：9 β-4- Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ-(2-プロペニリデン)-7,13- ビス- Ｏ- トリエチルシリルバッカチンIII
上記工程２で得た化合物 0.8413 g を乾燥したテトラヒドロフラン 40 mlに溶解させ、0 ℃で 1.0 mol/Lリチウムビストリメチルシリルアミド 3.1 ml ( テトラヒドロフラン溶液) を滴下し、15分後にシクロプロパンカルボニルクロリド 0.24 mlを添加した。45分後、0 ℃で飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。飽和食塩水で洗浄し、無水硫酸ナトリウムにて乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝10:1(v/v) →ヘキサン：酢酸エチル＝6:1(v/v)）で精製し、無色ガラス状の標記化合物 0.8104 g を得た。
【０５５２】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.33(3H,d,J=2.4Hz), 0.04(3H,d,J=2.4Hz), 0.57-0.75(12H,m),
0.97(9H,t,J=7.8Hz), 1.02(9H,t,J=7.8Hz), 1.13(3H,s), 1.20-1.46(2H,m),
1.52(3H,s), 1.56(3H,s), 1.64-1.76(1H,m), 1.87(3H,s),
2.02(1H,ddd,J=14.4Hz,J=10.4Hz,J=4.4Hz), 2.22-2.41(3H,m),
3.15(1H,d,J=5.4Hz), 3.88(1H,dd,J=10.4Hz,J=5.4Hz),
4.25(1H,d,J=8.3Hz), 4.34(1H,d,J=8.3Hz), 4.52-4.64(2H,m),
4.72(1H,dd,J=8.8Hz,J=4.4Hz), 4.97(1H,t,J=8.3Hz), 5.05(1H,d,J=5.7Hz),
5.28(1H,d,J=8.8Hz), 5.42(1H,d,J=10.3Hz), 5.53(1H,d,J=17.6Hz),
5.91(1H,d,J=5.4Hz), 6.13(1H,ddd,J=17.6Hz,J=10.3Hz,J=5.7Hz),
7.45(2H,t,J=7.4Hz), 7.56(1H,t,J=7.4Hz), 8.08(2H,d,J=7.4Hz).
【０５５３】
工程４：9 β-4- Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
上記工程３で得た化合物を原料に用い、参考例７の工程３と同様の反応操作を行うことにより、無色ガラス状の標記化合物を得た。
【０５５４】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.05-1.40(4H,m), 1.17(3H,s), 1.61(3H,s), 1.73-2.48(m), 1.92(3H,s),
3.04(1H,d,J=4.4Hz), 3.86(1H,d,J=6.9Hz), 4.03-4.18(1H,m),
4.36(1H,d,J=8.3Hz), 4.42(1H,d,J=8.3Hz), 4.57(1H,d,J=8.3Hz),
4.68-4.82(1H,m), 4.98(1H,s like), 5.22(1H,d,J=5.9Hz),
5.29(1H,d,J=6.9Hz), 5.45(1H,d,J=10.2Hz), 5.56(1H,d,J=17.1Hz),
5.94-6.11(2H,m), 7.48(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz),
8.13(2H,d,J=7.8Hz).
【０５５５】
工程５：9 β-4- Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-7-Ｏ- トリエチルシリルバッカチンIII
上記工程４で得た化合物を原料に用い、参考例５の工程１と同様の反応操作を行うことにより、無色ガラス状の標記化合物を得た。
【０５５６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.58-0.72(6H,m), 0.97(9H,t,J=7.8Hz), 1.06-1.39(4H,m), 1.10(3H,s),
1.56(3H,s), 1.62(3H,s), 1.74-1.88(2H,m), 1.98(3H,s),
1.98-2.21(3H,m), 2.28-2.44(2H,m), 3.16(1H,d,J=5.3Hz),
3.95(1H,dd,J=8.3Hz,J=5.9Hz), 4.30(1H,d,J=8.3Hz), 4.38(1H,d,J=8.3Hz),
4.54(1H,d,J=7.8Hz), 4.68-4.82(2H,m), 5.10(1H,d,J=5.8Hz),
5.33(1H,d,J=7.8Hz), 5.45(1H,d,J=10.3Hz), 5.56(1H,d,J=17.6Hz),
5.93(1H,d,J=5.3Hz), 6.16(1H,ddd,J=17.6Hz,J=10.3Hz,J=5.8Hz),
7.47(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz).
【０５５７】
参考例１２
【０５５８】
【化５２】
工程１：9 β-10-デアセチル-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ- イソプロピリデン-7,13-ビス- Ｏ- トリエチルシリルバッカチンIII
参考例８の工程１で得た化合物を原料に用い、参考例１１の工程１と同様の反応操作を行うことにより、無色ガラス状の標記化合物を得た。
【０５６０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.33(3H,d,J=2.9Hz), 0.04(3H,d,J=2.9Hz), 0.58-0.72(12H,m),
0.94-1.05(18H,m), 1.12(3H,s), 1.37(3H,s), 1.47(3H,s), 1.49(3H,s),
1.57(3H,s), 1.86(3H,s), 2.09-2.36(4H,m), 2.30(3H,s),
3.19(1H,d,J=5.9Hz), 3.91(1H,dd,J=8.8Hz,J=3.4Hz),
4.40(2H,AB type q,J=8.8Hz), 4.50(1H,d,J=8.8Hz), 4.57(1H,m),
4.83(1H,t,J=7.3Hz), 4.97(1H,t,J=8.3Hz), 5.40(1H,d,J=8.8Hz),
5.84(1H,d,J=5.4Hz), 7.46(2H,t,J=7.8Hz), 7.57(1H,t,J=7.8Hz),
8.09(2H,d,J=7.8Hz).
【０５６１】
工程２：9 β-4,10-ジデアセチル-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ- イソプロピリデン-7,13-ビス- Ｏ- トリエチルシリルバッカチンIII
上記工程１で得た化合物を原料に用い、参考例１１の工程２と同様の反応操作を行うことにより、無色ガラス状の標記化合物を得た。
【０５６２】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.27(3H,d,J=2.9Hz), 0.01(3H,d,J=2.9Hz), 0.58-0.83(12H,m),
0.93-1.10(18H,m), 1.08(3H,s), 1.39(3H,s), 1.46(3H,s), 1.55(3H,s),
1.77(3H,s), 1.84-2.40(4H,m), 2.51(1H,dd,J=15.1Hz,J=10.0Hz),
2.73(1H,d,J=5.9Hz), 3.03(1H,dd,J=15.1Hz,J=2.4Hz), 3.64(1H,s),
3.86(1H,dd,J=7.3Hz,J=2.9Hz), 4.05(1H,d,J=7.8Hz), 4.09(1H,d,J=6,8Hz),
4.43(1H,m), 4.52(1H,d,J=6.8Hz), 4.62-4.65(2H,m), 5.54(1H,d,J=7.3Hz),
5.57(1H,d,J=3.9Hz), 7.44(2H,t,J=7.8Hz), 7.55(1H,t,J=7.8Hz),
8.19(2H,d,J=7.8Hz).
【０５６３】
工程３：9 β-4- Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ- イソプロピリデン-7,13-ビス- Ｏ- トリエチルシリルバッカチンIII
上記工程２で得た化合物を原料に用い、参考例１１の工程３と同様の反応操作を行うことにより、無色ガラス状の標記化合物を得た。
【０５６４】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.32(3H,d,J=2.4Hz), 0.05(3H,d,J=2.4Hz), 0.58-0.71(12H,m),
0.94-1.04(18H,m), 1.16(3H,s), 1.21-1.36(4H,m), 1.38(3H,s),
1.48(3H,s), 1.53(3H,s), 1.55(3H,s), 1.71(1H,m), 1.87(3H,s),
2.05-2.38(4H,m), 3.13(1H,d,J=5.4Hz), 3.87(1H,dd,J=8.8Hz,J=3.4Hz),
4.20(2H,AB type q,J=7.8Hz), 4.41(1H,d,J=8.8Hz), 4.60(1H,m),
4.43(1H,t,J=6.3Hz), 4.99(1H,t,J=8.3Hz), 5.42(1H,d,J=8.8Hz),
5.88(1H,d,J=5.4Hz), 7.46(2H,t,J=7.8Hz), 7.57(1H,t,J=7.8Hz),
8.10(2H,d,J=7.8Hz).
FAB mass：899(MH+)
【０５６５】
工程４：9 β-4- Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチンIII
上記工程３で得た化合物を原料に用い、参考例７の工程３と同様の反応操作を行うことにより、無色ガラス状の標記化合物を得た。
【０５６６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.15-1.37(7H,m), 1.41(3H,s), 1.58(3H,s), 1.64(6H,s), 1.82-2.41(5H,m),
1.73(3H,s), 3.05(1H,d,J=4.9Hz), 3.82(1H,d,J=6.8Hz), 4.08(1H,br),
4.39(2H,AB type q,J=8.3Hz), 4.67(1H,br), 4.76(1H,t,J=7.2Hz),
4.99(1H,s), 5.59(1H,d,J=6.8Hz), 6.06(1H,d,J=4.9Hz),
7.48(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz), 8.13(2H,d,J=7.3Hz).
FAB mass：813(MH+)
【０５６７】
工程５：9 β-4- Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-7- Ｏ- トリエチルシリルバッカチンIII
上記工程４で得た化合物を原料に用い、参考例５の工程１と同様の反応操作を行うことにより、無色ガラス状の標記化合物を得た。
【０５６８】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.58-0.64(6H,m), 0.71-0.88(9H,m), 1.05-1.22(4H,m), 1.14(3H,s),
1.41(3H,s), 1.57(3H,s), 1.60(3H,s), 1.86-2.08(5H,m), 1.93(3H,s),
3.11(1H,d,J=4.9Hz), 4.09-4.27(2H,m), 4.50(2H,AB type q,J=7.8Hz),
4.71-4.80(2H,m), 5.53(1H,d,J=7.8Hz), 5.96(1H,d,J=4.8Hz),
7.48(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.15(2H,d,J=7.3Hz).
【０５６９】
参考例１３
【０５７０】
【化５３】
工程１：9 β-10-デアセチル-7- デオキシ-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ- イソプロピリデン-13-Ｏ- トリエチルシリルバッカチン III
実施例１０の工程３で得た化合物 470 mg を塩化メチレン 45 mlに溶解させ、0 ℃でピリジン 15 mlおよびトリフルオロメタンスルホン酸無水物 570μl を添加した。室温で１時間撹拌後、反応液を撹拌されているジエチルエーテル 100 ml および飽和重曹水 50 mlに注ぎ、ジエチルエーテルで抽出し、飽和食塩水で洗浄して無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝4:1(v/v)、途中から 2:1(v/v) に変更）で精製し、標記化合物 240 mg を白色固体として得、原料 107 mg を回収した。
【０５７２】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
0.57-0.74(6H,m), 1.01(9H,t,J=8.9Hz), 1.20(3H,s), 1.40(3H,s),
1.51(3H,s), 1.54(3H,s), 1.57(3H,s), 1.75(1H,s), 1.84(3H,s),
2.13(1H,dd,J=8.1,J=14.7Hz), 2.22(1H,dd,J=8.6,J=14.7Hz), 2.29(3H,s),
3.09(1H,d,J=6.2Hz), 4.14(1H,d,J=8.1Hz), 4.27-4.33(2H,m),
4.90(1H,d,J=4.3Hz), 4.97(1H,br t,J=8.8Hz), 5.48(1H,d,J=8.1Hz),
5.66(1H,dd,J=10.3,J=4.3Hz), 5.87(1H,d,J=6.2Hz), 6.08(1H,d,J=10.3Hz),
7.49(2H,t,J=7.8Hz), 7.60(1H,t,J=7.8Hz), 8.15(2H,d,J=7.8Hz).
【０５７３】
工程２：9 β-10-デアセチル-7- デオキシ-6,7- ジデヒドロ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
上記工程１で得た化合物を用い、実施例１の工程４と同様の反応操作を行うことにより、標記化合物を白色固体として得た。
【０５７４】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.13(3H,s), 1.42(3H,s), 1.53(3H,s), 1.54(3H,s), 1.59(3H,s),
1.75(1H,s), 1.91(3H,s), 2.09(1H,dd,J=6.8,J=15.2Hz),
2.20(1H,br d,J=7.8Hz), 2.34(1H,dd,J=8.8,J=15.2Hz), 2.35(3H,s),
3.22(1H,d,J=5.9Hz), 4.04(1H,d,J=7.4Hz), 4.26(1H,d,J=8.1Hz),
4.34(1H,d,J=8.1Hz), 4.72-4.87(1H,m), 4.83(1H,d,J=4.4Hz),
5.54(1H,d,J=7.4Hz), 5.66(1H,dd,J=10.3,J=4.4Hz), 5.93(1H,d,J=5.9Hz),
6.12(1H,d,J=10.3Hz), 7.48(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz),
8.18(2H,d,J=7.3Hz).
【０５７５】
参考例１４
【０５７６】
【化５４】
工程１：9 β-10-デアセチル-7- デオキシ-9- ジヒドロ-7α- フルオロバッカチン III
10- デアセチル-7- デオキシ-7α- フルオロバッカチンIII 26.1 mg をテトラヒドロフラン 1.5 ml に溶解させ、0 ℃でボラン−テトラヒドロフラン(1.0M テトラヒドロフラン溶液) 1.5 mlを添加した。0 ℃で６時間撹拌後、メタノール 3.0 ml を滴下し、室温で30分撹拌後、溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：アセトン＝3:1(v/v)）で精製し、標記化合物 30.8 mgを無色透明ガラス状物質として得た。
【０５７８】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.14(3H,s), 1.63(3H,s), 1.71(3H,s), 1.77(1H,s), 1.87-1.90(3H,m),
2.11(1H,dd,J=5.9,J=15.6Hz), 2.15-2.52(4H,m), 2.32(3H,s), 3.34(1H,s),
3.56(1H,d,J=4.9Hz), 4.06(1H,d,J=5.4Hz), 4.22(1H,d,J=8.3Hz),
4.42(1H,d,J=8.3Hz), 4.71(1H,dd,J=5.4,J=48.3Hz), 4.72-4.83(1H,m),
4.99(1H,d,J=7.8Hz), 5.27(1H,br s), 6.08(1H,d,J=4.9Hz),
7.48(2H,t,J=7.8Hz), 7.59(1H,t,J=7.8Hz), 8.11(2H,d,J=7.8Hz).
【０５７９】
工程２：9 β-10-デアセチル-7- デオキシ-9- ジヒドロ-7α- フルオロ-9,10-Ｏ- イソプロピリデンバッカチン III
上記工程１で得た化合物を用い、実施例１の工程２と同様の反応操作を行うことにより、標記化合物を無色透明ガラス状物質として得た。
【０５８０】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.12(3H,s), 1.43(3H,s), 1.49(3H,s), 1.59(3H,s), 1.65(3H,s),
1.75(1H,s), 1.98(3H,d,J=1.5Hz), 2.00-2.45(5H,m), 2.33(3H,s),
3.59(1H,d,J=5.2Hz), 4.30(1H,d,J=8.8Hz), 4.35(1H,d,J=8.8Hz),
4.61(1H,d,J=8.8Hz), 4.75-4.85(1H,m),
4.92(1H,ddd,J=3.4,J=10.3,J=45.9Hz), 4.94(1H,d,J=3.9Hz),
5.59(1H,d,J=8.8Hz), 5.89(1H,d,J=5.2Hz), 7.48(2H,t,J=7.4Hz),
7.61(1H,t,J=7.4Hz), 8.12(2H,d,J=7.4Hz).
【０５８１】
参考例１５
【０５８２】
【化５５】
工程１：10,13-ジ- Ｏ- ベンジルオキシカルボニル-10-デアセチル-7- Ｏ- トリフルオロメタンスルホニルバッカチン III
10,13-ジ- Ｏ- ベンジルオキシカルボニル-10-デアセチルバッカチンIII 470 mgを塩化メチレン 20 mlに溶解させ、0 ℃で 4- ジメチルアミノピリジン 700 mg およびトリフルオロメタンスルホン酸無水物 480μl を添加した。0 ℃で１時間撹拌後、反応液を撹拌されている酢酸エチル 50 mlおよび氷水 50 mlに注ぎ、酢酸エチルで抽出し、飽和重曹水で洗浄して無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；クロロホルム：酢酸エチル＝1:1(v/v)）で精製し、標記化合物 370 mg を白色固体として得た。
【０５８４】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.10(3H,s), 1.18(3H,s), 1.68(1H,s), 1.86(3H,s), 2.13(3H,d,J=1.5Hz),
2.18-2.45(3H,m), 2.28(3H,s), 2.78-2.93(1H,m), 3.94(1H,d,J=6.8Hz),
4.13(1H,d,J=8.3Hz), 4.33(1H,d,J=8.3Hz), 4.91(1H,d,J=8.3Hz),
5.20(1H,d,J=12.2Hz), 5.24(2H,s), 5.25(1H,d,J=12.2Hz),
5.50(1H,dd,J=7.3,J=10.3Hz), 5.67(1H,d,J=6.8Hz), 5.92(1H,t,J=8.1Hz),
6.48(1H,s), 7.27-7.39(10H,m), 7.48(2H,t,J=7.3Hz),
7.62(1H,t,J=7.3Hz), 8.05(2H,d,J=7.3Hz).
【０５８５】
工程２：10,13-ジ- Ｏ- ベンジルオキシカルボニル-10-デアセチル-7- デオキシ-7β,8β- メチレン-19-ノルバッカチン III
上記工程１で得た化合物 220 mg をテトラヒドロフラン 12 mlおよびアセトニトリル 12 mlに溶解させ、シリカゲル 6.0 gを添加し 60 ℃で24時間撹拌後、濾過によりシリカゲルを除き、酢酸エチル 50 mlおよび飽和重曹水 50 mlを添加し、酢酸エチルで抽出し、飽和食塩水で洗浄して無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝3:1(v/v)）で精製し、標記化合物 170 mg を白色固体として得た。
【０５８６】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.14(3H,s), 1.22(3H,s), 1.39(1H,br s), 1.58(1H,s), 1.60-1.70(1H,m),
1.94(3H,d,J=1.0Hz), 2.09(1H,d,J=16.1Hz), 2.23-2.40(3H,m),
2.23(3H,s), 2.45(1H,dt,J=16.1,4.4Hz), 4.01(1H,d,J=7.3Hz),
4.10(1H,d,J=8.8Hz), 4.29(1H,d,J=8.8Hz), 4.72(1H,d,J=3.9Hz),
5.17-5.30(4H,m), 5.63(1H,d,J=7.3Hz), 5.80-5.92(1H,m), 6.12(1H,s),
7.28-7.50(10H,m), 7.48(2H,t,J=7.3Hz), 7.61(1H,t,J=7.3Hz),
8.08(2H,d,J=7.3Hz).
【０５８７】
工程３：10- デアセチル-7- デオキシ-7β,8β- メチレン-19-ノルバッカチン III
上記工程２で得た化合物 170 mg をエタノール 10 mlに溶解させ、室温で 10%- パラジウム- 炭素 34.0 mlを添加し、水素雰囲気下１時間撹拌後、濾過し、溶媒を減圧留去し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝1:1(v/v)）で精製し、標記化合物 110 mg を白色固体として得た。
【０５８８】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.11(3H,s), 1.15(3H,s), 1.35-1.43(1H,m), 1.74(1H,dd,J=5.2,7.1Hz),
1.76(1H,s), 2.03(3H,d,J=1.0Hz), 2.07-2.15(2H,m), 2.27(3H,s),
2.20-2.40(2H,m), 2.45(1H,dt,J=15.6,4.4Hz), 4.06(1H,d,J=7.8Hz),
4.22(1H,d,J=1.0Hz), 4.23(1H,d,J=8.3Hz), 4.32(1H,d,J=8.3Hz),
4.75(1H,d,J=3.9Hz), 4.82-4.90(1H,m), 5.04(1H,s), 5.62(1H,d,J=7.8Hz),
7.49(2H,t,J=7.3Hz), 7.61(1H,t,J=7.3Hz), 8.13(2H,d,J=7.3Hz).
【０５８９】
工程４：9 β-10-デアセチル-7- デオキシ-9- ジヒドロ-7β,8β- メチレン-19-ノルバッカチン III
上記工程３で得た化合物を用い、参考例１４の工程１と同様の反応操作を行うことにより、標記化合物を無色透明ガラス状物質として得た。
【０５９０】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
0.92(1H,br s), 1.06-1.18(1H,m), 1.14(3H,s), 1.39-1.48(2H,m),
1.67(3H,s), 1.78(1H,s), 1.83(3H,s), 2.16(1H,d,J=4.9Hz), 2.19(3H,s),
2.34-2.40(1H,m), 2.43(1H,dd,J=9.3,15.9Hz), 2.53(1H,dd,J=7.1,15.9Hz),
2.61(1H,d,J=7.8Hz), 2.58-2.68(1H,m), 3.25(1H,d,J=7.8Hz),
3.87(1H,dd,J=5.4,7.8Hz), 4.18(1H,d,J=7.3Hz),
4.58(1H,dd,J=7.8,10.7Hz), 4.69(1H,d,J=7.3Hz), 4.70-4.80(1H,m),
5.27(1H,dd,J=4.4,5.4Hz), 5.55(1H,d,J=7.8Hz), 7.47(2H,t,J=7.3Hz),
7.58(1H,t,J=7.3Hz), 8.04(2H,d,J=7.3Hz).
【０５９１】
工程５：9 β-10-デアセチル-7- デオキシ-9- ジヒドロ-7β,8β- メチレン-9,10-Ｏ- イソプロピリデン-19-ノルバッカチン III
上記工程４で得た化合物を用い、実施例１の工程２と同様の反応操作を行うことにより、標記化合物を無色透明ガラス状物質として得た。
【０５９２】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.11(3H,s), 1.20-1.40(2H,m), 1.34(3H,s), 1.48(3H,s), 1,53(3H,s),
1.68-1.80(2H,m), 1.70(1H,s), 1.76(1H,t,J=5.3Hz), 1.92(3H,d,J=1.0Hz),
2.09(1H,d,J=5.4Hz), 2.22(3H,s), 2.37(1H,dd,J=8.3,15.6Hz),
2.47(1H,dd,J=7.3,15.6Hz), 2.70(1H,dt,J=14.7,8.3Hz),
3.31(1H,d,J=8.3Hz), 4.22(1H,d,J=7.8Hz), 4.40(1H,d,J=7.8Hz),
4.49(1H,d,J=7.8Hz), 4.57(1H,dd,J=8.2,9.2Hz), 4.75-4.85(1H,m),
5.49(1H,d,J=7.8Hz), 5.50(1H,d,J=8.3Hz), 7.43(2H,t,J=7.3Hz),
7.59(1H,t,J=7.3Hz), 8.05(2H,d,J=7.3Hz).
【０５９３】
参考例１６
【０５９４】
【化５６】
工程１：10- デアセチル-10-Ｏ- ホルミルバッカチン III
10- デアセチルバッカチン III 104 mg を N,N- ジメチルホルムアミド 1.0 ml に溶解させ、0 ℃で 4- ジメチルアミノピリジン 70.7 mgおよびトリフルオロメタンスルホン酸無水物 96.0 μl を添加した。0 ℃で１０分間撹拌後、反応液を撹拌されている酢酸エチル 10 mlおよび水 40 mlに注ぎ、酢酸エチルで抽出し、飽和食塩水で洗浄して無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：酢酸エチル＝1:2(v/v)）で精製し、標記化合物 94.3 mgを白色固体として得た。
【０５９６】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.11(3H,s), 1.12(3H,s), 1.60(3H,s), 1.69(3H,s), 1.80-2.40(5H,m),
2.29(3H,s), 2.53-2.62(1H,m), 3.89(1H,d,J=6.8Hz), 4.16(1H,d,J=8.7Hz),
4.31(1H,d,J=8.7Hz), 4.40-4.50(1H,m), 4.90(1H,br q,J=5.6Hz),
4.98(1H,d,J=7.9Hz), 5.64(1H,d,J=6.8Hz), 6.46(1H,s),
7.50(2H,t,J=7.2Hz), 7.61(1H,t,J=7.2Hz), 8.10(2H,d,J=7.2Hz),
8.22(1H,s)
【０５９７】
工程２：10- デアセチル-10-Ｏ- ホルミル-7- Ｏ-[(1- イミダゾリル) チオカルボニル] バッカチン III
上記工程１で得た化合物 23.8 mgを テトラヒドロフラン 0.50 mlに溶解させ、室温で、ベンゼン 0.50 ml、1,8-ジアザビシクロウンデセン 12.5 μl およびチオカルボニルイミダゾール 12.5 mgを添加した。室温で１時間撹拌後、反応液に酢酸エチル 10 mlおよび飽和塩化アンモニウム水溶液 10 mlを添加し、酢酸エチルで抽出し、飽和食塩水で洗浄して無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；クロロホルム：酢酸エチル＝1:1(v/v)）で精製し、標記化合物 21.4 mgを白色固体として得た。
【０５９８】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.13(3H,s), 1.18(3H,s), 1.64(3H,s), 1.85-2.45(4H,m), 1.96(3H,s),
2.34(3H,s), 2.49(1H,br s), 3.04(1H,ddd,J=7.1,J=9.3,J=14.3Hz),
4.12(1H,d,J=7.3Hz), 4.21(1H,d,J=8.6Hz), 4.38(1H,d,J=8.6Hz),
4.88(1H,br s), 5.04(1H,d,J=9.3Hz), 5.69(1H,d,J=7.3Hz),
6.26(1H,dd,J=7.1,J=10.5Hz), 6.40(1H,s), 7.00(1H,s),
7.50(2H,t,J=7.2Hz), 7.52(1H,s), 7.63(1H,t,J=7.2Hz), 7.99(1H,s),
8.12(2H,d,J=7.2Hz), 8.18(1H,s)
【０５９９】
工程３：10- デアセチル-7- デオキシ-10-Ｏ- ホルミルバッカチン III
上記工程２で得た化合物 140 mg をジオキサン 5.0 ml に溶解させ、室温でトリブチルスズヒドリド 280μl および 2,2'-アゾビスイソブチロニトリル 10.0 mgを添加した。75-80 ℃で４０分間撹拌後、反応液に酢酸エチル 10 ml、水 10 mlおよび飽和食塩水 10 mlを添加し、酢酸エチルで抽出し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝5:7(v/v)）で精製し、標記化合物 52.0 mg白色固体として得た。
【０６００】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.09(3H,s), 1.12(3H,s), 1.50-2.50(8H,m), 1.75(3H,s), 2.04(3H,s),
2.29(3H,s), 3.85(1H,d,J=7.3Hz), 4.19(1H,d,J=8.3Hz),
4.32(1H,d,J=8.3Hz), 4.85(1H,br s), 4.97(1H,dd,J=9.3,J=2.5Hz),
5.63(1H,d,J=7.3Hz), 6.60(1H,s), 7.49(2H,t,J=7.3Hz),
7.63(1H,t,J=7.3Hz), 8.12(2H,d,J=7.3Hz), 8.24(1H,s)
【０６０１】
工程４：10- デアセチル-7- デオキシバッカチン III
上記工程３で得た化合物 50.0 mgを 95 ％エタノール 2.0 ml に溶解させ、室温でヒドラジン水和物 200μl を添加し３０分間撹拌後、反応液に酢酸エチル 10 mlおよび７％塩酸 50 mlを添加し、酢酸エチルで抽出し、飽和重曹水で洗浄して無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残分をシリカゲル薄層クロマトグラフィー（展開溶媒；ヘキサン：酢酸エチル＝2:3(v/v)）で精製し、標記化合物 30.0 mgを白色固体として得た。
【０６０２】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.06(3H,s), 1.09(3H,s), 1.50-1.55(1H,m), 1.80(1H,s),
1.90-2.41(7H,m), 2.17(3H,s), 2.29(3H,s), 3.92(1H,d,J=7.3Hz),
4.17(1H,d,J=1.5Hz), 4.22(1H,d,J=8.3Hz), 4.33(1H,d,J=8.3Hz),
4.82-4.92(1H,m), 4.96(1H,dd,J=9.6,J=3.2Hz), 5.24(1H,d,J=1.5Hz),
5.62(1H,d,J=7.3Hz), 7.48(2H,t,J=7.3Hz), 7.61(1H,t,J=7.3Hz),
8.12(2H,d,J=7.3Hz)
【０６０３】
工程５：9 β-10-デアセチル-7- デオキシ-9- ジヒドロバッカチン III
上記工程４で得た化合物を用い、参考例１４の工程１と同様の反応操作を行うことにより、標記化合物を無色透明ガラス状物質として得た。
【０６０４】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.15(3H,s), 1.51(3H,s), 1.67(3H,s), 1.91(3H,s), 1.50-2.70(9H,m),
2.35(3H,s), 3.04(1H,d,J=4.9Hz), 3.14(1H,br d,J=6.8Hz),
3.75(1H,br s), 4.21(1H,d,J=8.3Hz), 4.37(1H,d,J=8.3Hz),
4.71(1H,br q,J=8.3Hz), 4.86(1H,br s), 5.45(1H,br s),
6.05(1H,d,J=4.9Hz), 7.48(2H,t,J=7.6Hz), 7.61(1H,t,J=7.6Hz),
8.14(2H,d,J=7.6Hz).
【０６０５】
工程６：9 β-10-デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ- イソプロピリデンバッカチン III
上記工程５で得た化合物を用い、実施例１の工程２と同様の反応操作を行うことにより、標記化合物を無色透明ガラス状物質として得た。
【０６０６】
1H-NMR(400 MHz,CDCl3/TMS) δ(ppm)
1.16(3H,s), 1.43(3H,s), 1.51(3H,s), 1.57(3H,s), 1.59(3H,s),
1.79(1H,s), 1.99(3H,s), 1.45-2.40(6H,m), 2.35(3H,s),
2.44(1H,d,J=5.3Hz), 3.10(1H,d,J=4.9Hz), 4.19(1H,d,J=7.6Hz),
4.27(1H,d,J=8.3Hz), 4.34(1H,d,J=8.3Hz), 4.70-4.84(1H,m),
4.86(1H,br s), 5.62(1H,d,J=7.6Hz), 5.97(1H,d,J=4.9Hz),
7.48(2H,t,J=7.3Hz), 7.60(1H,t,J=7.3Hz), 8.14(2H,d,J=7.3Hz).
【０６０７】
参考例１７
【０６０８】
【化５７】
工程１：9 β-10-デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
参考例１６の工程５で得た化合物 0.4800 g を塩化メチレン 9.6 ml に溶解させ、室温でアクロレインジエチルアセタール 0.69 mlとカンファースルホン酸 19 mgを添加した。20分後、0 ℃に冷却し、トリエチルアミンを加えて pH 8 とした。これを減圧濃縮し、得られた残分をシリカゲルカラムクロマトグラフィー（展開溶媒；クロロホルム：アセトン＝12：１(v/v) ）で精製し、白色ガラス状固体の標記化合物 0.1823 g を得た。
【０６１０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.15(3H,s), 1.48(3H,s), 1.59(3H,s), 1.72-2.22(4H,m), 1.96(3H,s),
2.22-2.40(1H,m), 2.33(3H,s), 2.55(1H,br d,J=8.8Hz),
3.06(1H,d,J=5.4Hz), 4.19(1H,d,J=6.9Hz), 4.23(1H,d,J=8.3Hz),
4.32(1H,d,J=8.3Hz), 4.77(1H,br), 4.84(1H,s), 5.23(1H,d,J=6.4Hz),
5.32(1H,d,J=6.9Hz), 5.44(1H,d,J=10.2Hz), 5.57(1H,d,J=15.2Hz),
5.92-6.13(2H,m), 7.46(2H,t,J=7.8Hz), 7.57(1H,t,J=7.8Hz),
8.13(2H,d,J=7.8Hz).
【０６１１】
工程２：9 β-10-デアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン)-13- Ｏ- トリエチルシリルバッカチンIII
上記工程１で得た化合物を原料に用い、参考例７の工程１と同様の反応操作を実施し、白色ガラス状固体の標記化合物を得た。
【０６１２】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
0.58-0.76(6H,m), 1.01(9H,s), 1.25(3H,s), 1.49(3H,s), 1.61(3H,s),
1.82-2.18(6H,m), 1.93(3H,s), 2.25(3H,s), 2.92(1H,d,J=4.9Hz),
4.14(1H,d,J=8.3Hz), 4.24(1H,d,J=7.3Hz), 4.34(1H,d,J=8.3Hz),
4.93-5.05(2H,m), 5.20(1H,d,J=6.4Hz), 5.28(1H,d,J=7.3Hz),
5.44(1H,d,J=10.7Hz), 5.56(1H,d,J=17.1Hz), 5.91-6.09(2H,m),
7.47(2H,t,J=7.8Hz), 7.58(1H,t,J=7.8Hz), 8.14(2H,d,J=7.8Hz).
【０６１３】
工程３：9 β-10-デアセチル-7- デオキシ-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ-(2-プロペニリデン)-13- Ｏ- トリエチルシリルバッカチンIII
上記工程２で得られた化合物を原料に用い、参考例１１の工程１と同様の反応操作を実施し、無色透明オイル状の標記化合物を得た。
【０６１４】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.28(3H,d,J=2.9Hz), 0.05(3H,d,J=2.9Hz), 0.59-0.78(6H,m),
1.02(9H,t,J=7.8Hz), 1.19(3H,s), 1.50-1.64(1H,m), 1.53(3H,s),
1.59(3H,s), 1.82-2.04(3H,m), 1.89(3H,s),
2.14(1H,dd,J=15.1Hz,J=8.3Hz), 2.26(3H,s),
2.33(1H,dd,J=15.1Hz,J=8.8Hz), 2.88(1H,d,J=4.8Hz),
4.17(1H,d,J=8.3Hz), 4.23(1H,d,J=7.3Hz), 4.30(1H,d,J=8.3Hz),
4.54-4.62(1H,m), 4.94(1H,s), 4.99(1H,t,J=8.3Hz), 5.19(1H,d,J=6.3Hz),
5.27(1H,d,J=7.3Hz), 5.42(1H,d,J=10.7Hz), 5.55(1H,d,J=17.1Hz),
5.92-6.06(2H,m), 7.45(2H,t,J=7.9Hz), 7.56(1H,t,J=7.9Hz),
8.14(2H,d,J=7.9Hz).
【０６１５】
工程４：9 β-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ-(2-プロペニリデン)-13- Ｏ- トリエチルシリルバッカチンIII
上記工程３で得た化合物を原料に用い、参考例１１の工程２と同様の反応操作を実施し、淡黄色透明オイル状の標記化合物を得た。
【０６１６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.26(3H,d,J=2.9Hz), 0.01(3H,d,J=2.9Hz), 0.68-0.87(6H,m),
1.03(3H,s), 1.05(9H,t,J=7.8Hz), 1.42(3H,s), 1.52(3H,s),
1.52-1.73(2H,m), 1.80(3H,s), 1.80-1.95(2H,m),
2.52(1H,dd,J=15.1Hz,J=9.7Hz), 2.71(1H,d,J=4.4Hz),
2.85(1H,dd,J=15.1Hz,J=2.4Hz), 3.61(1H,s), 4.12-4.31(1H,m),
4.14(1H,d,J=7.3Hz), 4.18(1H,d,J=7.3Hz), 4.25(1H,d,J=7.3Hz),
4.57-4.70(3H,m), 5.20(1H,d,J=6.3Hz), 5.36(1H,d,J=7.3Hz),
5.43(1H,d,J=10.3Hz), 5.55(1H,d,J=17.1Hz), 5.93-6.08(2H,m),
7.44(2H,t,J=7.3Hz), 7.54(1H,t,J=7.3Hz), 8.17(2H,d,J=7.3Hz).
【０６１７】
工程５：9 β-4- Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-1- Ｏ- ジメチルシリル-9,10-Ｏ-(2-プロペニリデン)-13- Ｏ- トリエチルシリルバッカチンIII
上記工程４で得た化合物を原料に用い、参考例１１の工程３と同様の反応操作を実施し、白色ガラス状の標記化合物を得た。
【０６１８】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.28(3H,d,J=3.0Hz), 0.05(3H,d,J=3.0Hz), 0.56-0.80(6H,m),
1.02(9H,t,J=7.8Hz), 1.03-1.40(4H,m), 1.21(3H,s), 1.50-2.10(5H,m),
1.51(3H,s), 1.60(3H,s), 1.90(3H,s), 2.30(2H,d,J=8.8Hz),
2.83(1H,d,J=4.9Hz), 4.16(1H,d,J=8.3Hz), 4.22(1H,d,J=7.4Hz),
4.32(1H,d,J=8.3Hz), 4.60-4.72(1H,m), 4.89(1H,s), 5.01(1H,t,J=8.3Hz),
5.20(1H,d,J=8.3Hz), 5.26(1H,d,J=7.4Hz), 5.43(1H,d,J=10.3Hz),
5.55(1H,d,J=17.6Hz), 5.92-6.06(2H,m), 7.45(2H,t,J=7.9Hz),
7.57(1H,t,J=7.9Hz), 8.11(2H,d,J=7.9Hz).
【０６１９】
工程６：9 β-4- Ｏ- シクロプロパンカルボニル-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
上記工程５で得た化合物を原料に用い、参考例７の工程３と同様の反応操作を実施し、白色ガラス状の標記化合物を得た。
【０６２０】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.08-1.24(3H,m), 1.17(3H,s), 1.34-1.41(1H,m), 1.47(3H,s),
1.60(3H,s), 1.60-1.94(5H,m), 1.97(3H,s), 2.04-2.12(1H,m),
2.37(1H,d,J=9.8Hz), 2.40(1H,d,J=11.7Hz), 3.07(1H,d,J=5.4Hz),
4.18(1H,d,J=6.8Hz), 4.27(1H,d,J=8.7Hz), 4.36(1H,d,J=8.7Hz),
4.69-4.82(2H,m), 5.23(1H,d,J=6.3Hz), 5.33(1H,d,J=10.2Hz),
5.57(1H,d,J=17.1Hz), 5.96-6.08(2H,m), 7.48(2H,t,J=7.3Hz),
7.60(1H,t,J=7.3Hz), 8.15(2H,d,J=7.3Hz).
【０６２１】
参考例１８
【０６２２】
【化５８】
工程１：9 β-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-1- Ｏ- ジメチルシリル-4- Ｏ- エトキシカルボニル-9,10-Ｏ-(2-プロペニリデン)-13- Ｏ- トリエチルシリルバッカチンIII
参考例１７の工程４で得た化合物を原料に用い、シクロプロパンカルボニルクロリドの代わりにクロロギ酸エチルを使用し、参考例１１の工程３と同様の反応操作を実施した。これにより、無色透明オイル状の標記化合物を得た。
【０６２４】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
-0.28(3H,d,J=2.9Hz), 0.03(3H,d,J=2.9Hz), 0.56-0.75(6H,m),
1.00(9H,t,J=7.8Hz), 1.22(3H,s), 1.39(3H,t,J=7.3Hz), 1.50-1.70(2H,m),
1.52(3H,s), 1.60(3H,s), 1.75-2.10(2H,m), 1.89(3H,s),
2.20-2.37(2H,m), 2.80(1H,d,J=4.4Hz), 4.15-4.26(3H,m),
4.36-4.44(2H,m), 4.60-4.68(1H,m), 4.98-5.04(2H,m),
5.20(1H,d,J=6.3Hz), 5.26(1H,d,J=7.3Hz), 5.43(1H,d,J=10.3Hz),
5.55(1H,d,J=17.1Hz), 5.91-6.07(2H,m), 7.45(2H,t,J=7.8Hz),
7.55(1H,t,J=7.8Hz), 8.13(2H,d,J=7.8Hz).
【０６２５】
工程２：9 β-4,10-ジデアセチル-7- デオキシ-9- ジヒドロ-4- Ｏ- エトキシカルボニル-9,10-Ｏ-(2-プロペニリデン) バッカチンIII
上記工程１で得た化合物を原料に用い、参考例７の工程３と同様の反応操作を実施し、白色ガラス状の標記化合物を得た。
【０６２６】
1H-NMR(400 MHz, CDCl3/TMS) δ(ppm)
1.16(3H,s), 1.43(3H,t,J=7.3Hz), 1.48(3H,s), 1.54-2.15(5H,m),
1.60(3H,s), 1.97(3H,s), 2.37(1H,dd,J=15.7Hz,J=9.8Hz),
2.50(1H,d,J=10.3Hz), 3.00(1H,d,J=4.9Hz), 4.10-4.40(5H,m),
4.65-4.80(1H,m), 4.89(1H,s), 5.23(1H,d,J=6.3Hz), 5.34(1H,d,J=6.9Hz),
5.46(1H,d,J=10.2Hz), 5.57(1H,d,J=17.1Hz), 5.92-6.08(2H,m),
7.47(2H,t,J=7.8Hz), 7.58(1H,t,J=7.8Hz), 8.14(2H,d,J=7.8Hz).
【０６２７】
【発明の効果】
次の実験例により、本発明化合物の抗腫瘍効果を示す。
実験例
３種の腫瘍細胞、P388、PC-6および PC-12をそれぞれ、P388は 5.0×102 cells/150 μl/well、PC-6は 5.0×103 cells/150 μl/well、 PC-12 は 1.0×103 cells/150 μl/wellになるように 96 ウェル−マイクロプレートに播種し、P388は２時間後、ほかの２つは、24時間後に検体を 50 μl/well添加した。その後、３日間培養し、ＭＴＴ[3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide]の 5 mg/ml溶液を 20 μl/well添加した。４時間後培養液を除去し、ジメチルスルホキシドを 150μl/well加え、吸光度を 540 nm にて測定した。抗腫瘍効果は薬剤添加群の細胞増殖を対照群の 50 % にする薬剤濃度を GI50 値 (ng/ml)として示した。
【０６２８】
【表８】
[Industrial application fields]
The present invention relates to a novel taxol derivative having antitumor activity.
[0002]
[Prior art]
Taxol is a natural product represented by the chemical structural formula shown in Chemical Formula 7 and is obtained in a trace amount from the trunk of a yew tree.
[0003]
[Chemical 7]
Taxol is known to have antitumor activity, but its mechanism of action is based on the depolymerization inhibitory action of microtubules in cell division, and is a different type of antitumor from conventional antitumor agents Its clinical application is expected as an agent.
[0005]
Until now, only a very small amount of taxol was obtained from nature. However, 10-O-deacetylbaccatin III which is a taxol precursor represented by Chemical formula 8 which can be obtained in relatively large amounts from yew leaves and the like.
[0006]
[Chemical 8]
Taxol derivatives synthesized using as a raw material have begun to be reported (see JP-A-03-505725). Among them, a compound having a structure represented by Chemical Formula 9 (Taxotere) has been attracting attention as a compound having an antitumor activity equivalent to or higher than that of Taxol, and is currently being developed as an antitumor agent.
[0008]
[Chemical 9]
[Problems to be solved by the invention]
Taxol and compounds represented by Chemical Formula 9 are promising as antitumor agents. However, clinical trials have proved to be less effective for digestive organ cancer, particularly colon cancer, and a derivative having a stronger antitumor effect is desired.
[0010]
[Means for Solving the Problems]
Usually, the 9-position of a taxol derivative is a keto group, but some derivatives in which this moiety is reduced are also known. Compounds having an α-position hydroxyl group at the 9-position are obtained from nature, and various 9-position α-hydroxyl derivatives derived from this have been reported (for example, J. Med. Chem.,).372655 (1994)). Further, it is known that a compound having a β-position hydroxyl group at the 9-position can be chemically synthesized by reducing 10-O-deacetylbaccatin III using a reducing agent. Various reports have been made (for example, WO94 / 20088). As a result of intensive studies, the present inventors have found that the antitumor activity is significantly increased by converting the 9-position hydroxyl group and the 10-position hydroxyl group of the 9-position β-hydroxyl taxol derivative into a cyclic acetal type. completed.
[0011]
The present invention relates to general formula (I)
[0012]
Embedded image
[Where:
R1 Means a phenyl group, and the phenyl group may have one or more substituents selected from the group consisting of a halogen atom, an alkyl group and an alkoxyl group.
[0014]
R2 Means an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an alkoxyl group. These alkyl group, alkenyl group, alkynyl group, cycloalkyl group and alkoxyl group are a halogen atom, a hydroxyl group, a carboxyl group, an alkoxyl group, an aryl group. It has one or more substituents selected from the group consisting of oxy group, phenyl group, amino group, alkylamino group, alkoxycarbonyl group, aryloxycarbonyl group, acyl group, acylamino group and acyloxy group. Also good.
[0015]
RThree Is a hydrogen atom, a hydroxyl group, a halogen atom, an alkoxyl group, a group —O—R31An acyloxy group or a group -O-CO-R31The alkoxyl group and the acyloxy group are a halogen atom, a hydroxyl group, a carboxyl group, a cycloalkyl group, an alkoxyl group, an aryl group, an aryloxy group, an amino group, an alkylamino group, an alkoxycarbonyl group, an aryloxycarbonyl group, Substituting a group selected from the group consisting of an acyl group, an acylamino group, an acyloxy group and a heterocyclic group (the heterocyclic group may have one or more alkyl groups on the constituent atoms of the ring) You may have one or more as a group.
(Where R31Means an alkylamino group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group. These alkylamino groups, alkenyl groups, alkynyl groups, cycloalkyl groups, aryl groups and heterocyclic groups are halogen atoms, hydroxyl groups, carboxyl groups, alkyl groups, alkoxyl groups, aryloxy groups, phenyl groups, amino groups, alkyl groups. An amino group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group, an acyloxy group, and a nitrogen-containing heterocyclic group having a size of 3 to 8 members (the nitrogen-containing group) A heterocyclic group may have one or more alkyl groups on the constituent atoms of the ring as substituents. )
RThree May form a three-membered ring with a methyl group bonded to a carbon atom adjacent to the carbon atom to which it is bonded.
[0016]
RFour And RFive Each independently represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic group, and these alkyl group, alkenyl group, alkynyl group, aryl group and heterocyclic group represent an alkoxyl group, an amino group Groups, alkylamino groups, aminoalkyl groups, alkylaminoalkyl groups and formulas
[0017]
Embedded image
And a saturated heterocyclic group having a size of 5 to 6 members containing a nitrogen atom (the heterocyclic group may have an alkyl group on a carbon atom which is a constituent atom of the ring). May be substituted with a group selected from the group consisting of:
[0018]
Z1 Means a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group,
Z2 Means a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group,
ZThree Means an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group. These alkyl group, alkenyl group, alkynyl group, cycloalkyl group, aryl group and heterocyclic group are a halogen atom, a hydroxyl group , Carboxyl group, alkyl group, alkoxyl group, phenyl group, amino group, alkylamino group, aminoalkyl group, alkylaminoalkyl group, alkoxycarbonyl group, aryloxycarbonyl group, acyl group, acylamino group, and acyloxy group One or more selected groups may be substituted.
[0019]
ZFour Means an alkyl group, an aryl group or an alkoxyl group. These alkyl group, aryl group and alkoxyl group are a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxyl group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group. One or a plurality of groups selected from the group consisting of a group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group, and an acyloxy group may be included.
[0020]
In addition,
[0021]
Embedded image
And a salt thereof.
[0022]
The present invention also relates to a compound of the general formula (Ia)
[0023]
Embedded image
And a salt thereof.
[0024]
Next, terms used in this specification will be described.
[0025]
As used here, “C1 ~ C6 "Means one having 1 to 6 carbon atoms, for example," C2 ~ C6 “Alkenyl group” means an alkenyl group having 2 to 6 carbon atoms.
[0026]
The “alkyl group”, “alkenyl group” and “alkynyl group” may be linear or branched, and those having 1 to 6 carbon atoms (in the case of alkenyl and alkynyl groups) to 6 carbon atoms are preferred.
[0027]
An “alkoxyl group” means a group in which an alkyl group is bonded to the group —O—, and the alkyl group may be substituted with a phenyl group (which may have a substituent). Specific examples include benzyloxy, phenethyloxy, p-methoxybenzyloxy and the like. The alkyl moiety preferably has 1 to 6 carbon atoms.
[0028]
“Alkoxycarbonyl group” means an alkyl group bonded to an oxygen atom of a group —COO—, and this alkyl group may be substituted with a phenyl group (which may have a substituent). Often, such examples include benzyloxycarbonyl, phenethyloxycarbonyl, p-methoxybenzyloxycarbonyl, and the like. The alkyl moiety preferably has 1 to 6 carbon atoms.
[0029]
“Aryl group” means a monovalent group obtained by removing one hydrogen atom from an aromatic hydrocarbon nucleus, and examples thereof include phenyl, tolyl, biphenylyl, naphthyl and the like.
[0030]
The bonding position of the amino group of the “aminoalkyl group” may be any position of the alkyl group. Further, the alkyl group preferably has 1 to 6 carbon atoms.
[0031]
“Alkylamino group” means an amino group substituted with one alkyl group, or an amino group substituted with two alkyl groups (the two alkyl groups may be the same or different). . Further, the alkyl group preferably has 1 to 6 carbon atoms.
[0032]
“Acyl group” means a carbonyl group (—CO—) bonded with a hydrogen atom, an alkyl group or an aryl group, and examples thereof include formyl, acetyl, propanoyl, benzoyl and the like. The alkyl group to be bonded preferably has 1 to 6 carbon atoms, and the aryl group to be bonded is preferably a phenyl group.
[0033]
“Heterocyclic group” means a monocyclic or bicyclic saturated group containing one or more atoms selected from the group consisting of oxygen, nitrogen and sulfur atoms as constituent atoms of the ring structure. Alternatively, it means a substituent derived from an unsaturated heterocyclic compound, and these heterocyclic groups may be bonded at any position. Examples of monocyclic heterocyclic groups include pyrrole, furan, thiophene, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, imidazole, pyrazole, imidazolidine, pyrazolidine, oxazole, thiazole, oxadiazole, thiadiazole, pyridine, dihydropyridine, tetrahydropyran And substituents derived from monocyclic heterocyclic compounds such as piperidine, pyridazine, pyrimidine, pyrazine, piperazine, dioxane, pyran and morpholine. Examples of the bicyclic heterocyclic group include substituents derived from bicyclic heterocyclic compounds such as benzofuran, indolizine, benzothiophene, indole, naphthyridine, quinoxaline, quinazoline, and chroman.
[0034]
“Nitrogen-containing heterocyclic group” means that at least one nitrogen atom is included as a constituent atom of the heterocyclic group, and at least one atom selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom is included as a constituent atom. It means a substituent derived from a saturated or unsaturated heterocyclic compound which may contain one or more. Examples include pyrrole, pyrrolidine, imidazole, pyrazole, imidazolidine, pyrazolidine, oxazole, thiazole, oxadiazole, thiadiazole, pyridine, dihydropyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, thiomorpholine, and the like.
[0035]
"formula
[0036]
Embedded image
(X is oxygen atom, sulfur atom, CH2, CH—Y, NH or N—Y, Y represents an alkyl group. )
And a saturated heterocyclic group having a size of 5 to 6-membered ring containing a nitrogen atom (wherein the heterocyclic group has one or more alkyl groups on a carbon atom that is a constituent atom of the ring) The term "" means a substituent derived from a saturated heterocyclic compound having a size of 5 to 6 members and always containing one nitrogen atom as a constituent atom of the heterocyclic group. Examples thereof include pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, thiazolidine, isoxazolidine, isothiazolidine, piperidine, piperazine, morpholine, thiomorpholine, and the like.
[0038]
RThree But RThree Forming a 3-membered ring with a methyl group bonded to a carbon atom adjacent to the carbon atom to which is bonded means that the 7-position and 8-position moieties have the following structure.
[0039]
Embedded image
Next, each substituent in the general formula (I) will be described.
[0041]
R1 The “alkyl group” and the “alkoxyl group” as the substituent of the phenyl group are preferably those having 1 to 3 carbon atoms.
[0042]
R1 The number of substituents of the phenyl group is preferably 1 or 2, and the substitution position of the substituent is preferably the meta position.
[0043]
R1 Is preferably an unsubstituted phenyl group. In addition, a phenyl group in which one or two fluorine atom, chlorine atom, methyl group or methoxy group is substituted at the meta position is also preferable.
[0044]
R2 As these, an alkyl group, an alkoxyl group and a cycloalkyl group are preferable.
[0045]
R2 As the “alkyl group” of C,1 ~ C6 An alkyl group is preferable, and a methyl group, an ethyl group, and a propyl group are particularly preferable.
[0046]
R2 As the “alkoxyl group” of C,1 ~ C6 An alkoxyl group is preferable, and a methoxy group and an ethoxy group are particularly preferable.
[0047]
R2 As the “cycloalkyl group”,Three ~ C6 A cycloalkyl group is preferred, and a cyclopropyl group is particularly preferred.
[0048]
R2 As a methyl group, an ethyl group, a propyl group, a methoxy group, an ethoxy group or a cyclopropyl group is particularly preferable.
[0049]
RThree As the “halogen atom”, a fluorine atom is preferable.
[0050]
RThree Is particularly preferably a hydrogen atom, a fluorine atom or a hydroxyl group. RThree As RThree Formed a 3-membered ring with a methyl group bonded to the carbon atom (position 8) adjacent to the carbon atom (position 7) to which is bonded, that is, the 7-position and 8-position portions have the following structure A thing is also mentioned as a preferable example.
[0051]
Embedded image
RFour And RFive The alkyl group is preferably an alkyl group having 1 to 6 carbon atoms, particularly preferably a methyl group, an ethyl group, or a propyl group.
[0053]
RFour And RFive As the alkenyl group, those having 2 to 6 carbon atoms are preferable, and an allyl group is particularly preferable.
[0054]
RFour And RFive As the substituent of the alkyl group, alkenyl group or phenyl group, an amino group, an alkylamino group, or a formula
[0055]
Embedded image
And a saturated heterocyclic group having a size of a 5-membered or 6-membered ring containing a nitrogen atom (the heterocyclic group may have an alkyl group on a carbon atom which is a constituent atom of the ring) Is good).
[0056]
The alkyl part of the alkylamino group is C1 ~ CThree Alkyl groups are preferred and may be dialkyl substituted. (In the case of dialkyl substitution, the two alkyl groups may be the same or different.)
The formula
[0057]
Embedded image
[0058]
Moreover, as an alkyl group substituted on the carbon atom which is a constituent atom of the ring of a heterocyclic group, a methyl group is preferable.
[0059]
RFour And RFive Preferable examples include a combination in which the other is a hydrogen atom or an alkyl group and the other is an alkyl group, an alkenyl group or a phenyl group.
[0060]
Z1 And Z2 As the “halogen atom”, a fluorine atom, a chlorine atom and a bromine atom are preferable.
[0061]
Z1 And Z2 As the “alkyl group”, a methyl group, an ethyl group, or a propyl group is preferable.
[0062]
Z1 Is preferably a halogen atom or a hydroxyl group, and among the halogen atoms, a fluorine atom is particularly preferred.
[0063]
Z2 Is preferably a halogen atom, a hydrogen atom or an alkyl group. Of the halogen atoms, a fluorine atom is particularly preferable. Among the alkyl groups, a methyl group is particularly preferable.
[0064]
Z1 And Z2 Most preferred as Z1 Is a fluorine atom, Z2 Is a combination of fluorine atoms, Z1 Is a hydroxyl group, Z2 Is a combination of hydrogen atoms, or Z1Is a hydroxyl group, Z2Is a combination of methyl groups.
[0065]
ZThree Is preferably an aryl group, a heterocyclic group or an alkenyl group.
[0066]
ZThree As the “aryl group”, a phenyl group is preferable.
[0067]
ZThreeAs the “alkenyl group”, 2-methyl-1-propenyl is preferable.
[0068]
ZThree The heterocyclic group is preferably a monocyclic heterocyclic group, more preferably a monocyclic 5-membered or 6-membered heterocyclic group, such as pyrrole, furan, thiophene, pyrrolidine, tetrahydrofuran, Examples include tetrahydrothiophene, imidazole, pyrazole, imidazolidine, pyrazolidine, oxazole, thiazole, oxadiazole, thiadiazole, pyridine, dihydropyridine, tetrahydropyran, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, dioxane, pyran, morpholine and the like.
[0069]
ZThree Among these heterocyclic groups, a monocyclic five-membered or six-membered heterocyclic group, particularly preferably a heterocyclic group containing one oxygen atom, nitrogen atom or sulfur atom as a constituent atom of the ring structure, , Pyrrole, furan, thiophene, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, pyridine, dihydropyridine, tetrahydropyran, piperidine, pyran and the like.
[0070]
ZThree Among these heterocyclic groups, monocyclic 5-membered or 6-membered heterocyclic groups are most preferably unsaturated heterocyclic groups containing one oxygen atom, nitrogen atom or sulfur atom as a constituent atom of the ring structure. Specific examples thereof include groups derived from furan, pyridine, and pyrrole.
[0071]
ZThree As such, 2-methyl-1-propenyl group, phenyl group, furyl group, pyridyl group and pyrrolyl group are particularly preferable.
[0072]
ZFour Is preferably an aryl group or an alkoxyl group.
[0073]
ZFourAs the “aryl group”, a phenyl group is preferable.
[0074]
ZFour As the “alkoxyl group”, tertiary butoxy is preferable.
[0075]
ZFour Are particularly preferably a phenyl group and a tertiary butoxy group.
[0076]
In the present invention, the configuration shown in Chemical Formula 19 is preferred.
[0077]
Embedded image
Substituent ZThreeThe configuration at the 3 ′ position to which is attached includes both configurations, but the configuration having the same configuration as natural taxol is more preferable. The 7-position configuration includes both α and β configurations.
[0079]
The taxol derivative of the present invention may be a free form, but may be an acid addition salt or a carboxyl group salt. Examples of acid addition salts include inorganic acid salts such as hydrochloride, sulfate, nitrate, hydrobromide, hydroiodide, phosphate, acetate, methanesulfonate, benzene Examples thereof include organic acid salts such as sulfonate, toluenesulfonate, citrate, maleate, fumarate, and lactate.
[0080]
Examples of the carboxyl group salt include alkali metal salts such as lithium salt, sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, ammonium salt, triethylamine salt and N-methylglucamine salt. Any of inorganic salts and organic salts such as tris- (hydroxylmethyl) aminomethane salt may be used.
[0081]
A method for producing the compound of the present invention will be described. In the reaction, the substituent is protected with a protecting group as necessary, and the conversion order of each substituent is not particularly limited.
[0082]
Embedded image
Embedded image
R13Is RThreeOr R protected by a protecting groupThree(RThreeIs substituted with a hydroxyl group or an amino group, or RThreeIs a hydroxyl group).
R14Is RFourOr R protected by a protecting groupFour(RFourIs substituted with an amino group or the like.
R15Is RFiveOr R protected by a protecting groupFive(RFiveIs substituted with an amino group or the like.
Z11Is Z1Z protected by a protecting group1(Z1Is a hydroxyl group).
Ztwenty oneIs Z2Z protected by a protecting group2(Z2Is a hydroxyl group).
Z31Is ZThreeZ protected by a protecting groupThree(ZThreeIs substituted with a hydroxyl group or an amino group.
Z41Is ZFourZ protected by a protecting groupFour(ZFourIs substituted with a hydroxyl group or an amino group.
R8And R9Each independently represents a hydrogen atom, an alkyl group, an aryl group or the like, and preferably both are methyl groups or one is a p-methoxyphenyl group and the other is a hydrogen atom.
RTenAnd R11Represents a protecting group for a hydroxyl group.
[0085]
Compound (2) derivable from 10-O-deacetylbaccatin III (1) and R14C (= O) R15An aldehyde or ketone represented by14R15C (OR45)2 (R45Represents an alkyl group such as a methyl group. ) Compound (3) can be obtained by reacting acetal in the presence of an acidic catalyst such as 10-camphorsulfonic acid or p-toluenesulfonic acid. Subsequently, compound (4) can be obtained by condensing compound (A), (B) or (C) with the hydroxyl group at position 13 of compound (3) by a method reported in the literature.
[0086]
As the condensation reaction using the compound (A) or (B), a method using a carboxylic acid activator such as di (2-pyridyl) carbonate or dicyclohexylcarbodiimide in the presence of a base catalyst such as 4-dimethylaminopyridine. It has been known. In addition, when compound (A) is used, Z11And Ztwenty oneIs a combination of a hydrogen atom and a hydroxyl group.
[0087]
As a condensation reaction using the compound (C), a method using a base such as sodium hexamethyldisilazide is known.
[0088]
At this time, the compound (A), (B) or (C) may react with the hydroxyl group at the 7-position of the compound (3). In such a case, it may be separated and purified by a method such as silica gel column chromatography. However, by appropriately selecting the kind of the protecting group and the reaction conditions, compound (5) in which a protecting group is selectively introduced into the 7-position of compound (3) can be obtained (particularly in the case of carbamate type protecting groups). High selectivity is obtained. For example, by reacting 2,2,2-trichloroethoxycarbonyl chloride in pyridine with cooling at 0 ° C., the 7-position is selectively protected with a 2,2,2-trichloroethoxycarbonyl group. The compound (4) may be synthesized by condensing the compound (A), (B) or (C) with the hydroxyl group at the 13-position of the compound (5) in the same manner as described above. Further, after converting the hydroxyl group at the 13-position of the compound (3) to a ketone with an oxidizing agent such as manganese dioxide, a protecting group is introduced into the hydroxyl group at the 7-position to synthesize the compound (6), and again sodium borohydride, etc. There is also a method in which the compound (5) is obtained by reducing the ketone at the 13-position to a hydroxyl group using a reducing agent.
[0089]
Each substituent of the compound (4) thus obtained is converted or deprotected as necessary to convert the benzoyl group at the 2-position to COR.1 And the acetyl group at position 42 And the 7-position hydroxyl group to RThree And R14, R15, Z11, Ztwenty one, Z31And Z41Each RFour , RFive , Z1 , Z2 , ZThree And ZFour To obtain the target compound (I). These transformations and deprotections can be carried out using ordinary organic chemical methods, but examples are given below.
[0090]
The benzoyl group at the 2-position is COR1 As a method of converting into, for example, literature (Tetrahedron Lett.,35, 8931 (1994)), there is a method in which the ester bond at the 2-position is selectively hydrolyzed and then acylated.1 Can obtain compounds other than phenyl groups.
[0091]
The acetyl group at position 4 is COR2 As a method for converting to R, in the presence of a base such as sodium hexamethyldisilazide, Rtwenty one-X (Rtwenty oneRepresents an alkyl group, an alkenyl group or an aryl group, and X represents a halogen atom such as an iodine atom or a bromine atom, or a leaving group such as a methanesulfonyl group or a paratoluenesulfonyl group) There is a method of reacting from 100 ° C. to room temperature, R2 Can obtain compounds other than methyl groups.
[0092]
In addition, compound (6) is prepared in the presence of a base such as sodium hexamethyldisilazide.twenty oneBy reacting with a compound represented by -X, the 4-position acetyl group is converted to COR.2 By converting the hydroxyl group at position 13 and subsequently condensing with (A), (B) or (C).2 Can obtain compounds other than methyl groups.
[0093]
R at the 7-position hydroxyl groupThree R can be converted to RThree There are various methods depending on the type. 7-position hydroxyl group is known in the literature (for example, J. Org. Chem.,58, 5028 (1993)) to remove RThree A compound in which is hydrogen can be obtained. By acylating the hydroxyl group at the 7-position with a carboxylic acid or acid chloride by a conventional organic chemical method, RThree Is -OC (= O) R31Can be obtained. ClC (= O) OR at the 7th hydroxyl group32(R32Is an aryl group such as a paranitrophenyl group), a method in which an amine is reacted, a method in which phosgene is allowed to act in the presence of an amine, ClC (═O) NQ1Q2(Q1And Q2Each independently represents a hydrogen atom or an alkyl group. ) Or R31In a method of reacting an isocyanate represented by N═C═O, RThree Is -OC (= O) NQ1Q2(Q1And Q2Each independently represents a hydrogen atom or an alkyl group. ) Can be obtained. In addition, after converting the hydroxyl group at the 7-position, organic chemical conversion in several steps is performed to obtain the target RThree Can also be converted.
[0094]
In addition, the hydroxyl group at the 13-position of compound (5)TenProtecting group R distinguishable from11After protecting with RTenWas removed to obtain compound (8), and the hydroxyl group at the 7-position of compound (8) was converted to R in the same manner as above.13 After conversion to the protecting group R11Can be removed to obtain compound (9). Subsequently, the compound (A), (B) or (C) is condensed with the hydroxyl group at the 13-position of the compound (9), and finally, the target compound (I) is subjected to conversion and deprotection of various substituents. Can be obtained. Compound (8) is a protecting group R11The compound (3) can also be directly synthesized from the compound (3) by converting the hydroxyl group at the 7-position by appropriately selecting reaction conditions.
[0095]
RThree A target compound in which is a halogen atom, for example RThree Is a fluorine atom by treating a compound in which the 7-position is a hydroxyl group with diethylaminosulfur trifluoride in tetrahydrofuran, methylene chloride, ethyl ether, toluene, 1,1-dimethoxyethane or a mixed solvent thereof. Obtainable.
[0096]
Compound (8) can also be synthesized from compound (D) obtained from compound (1). Protecting group R that can be distinguished from 2,2,2-trichloroethoxycarbonyl group at the hydroxyl group at position 13 of compound (D)11Then, the 9th-position ketone is converted into a hydroxyl group by treating the compound obtained by removing the 2,2,2-trichloroethoxycarbonyl groups at the 7- and 10-positions with a reducing agent such as tetrabutylammonium borohydride. Then, the compound (8) can be obtained by reacting with aldehyde, ketone or acetal in the same manner as described above.
[0097]
The following compounds as manufacturing raw materials can be synthesized by reported methods.
Compound (2) WO 94/20088 etc.
Compound (D) tetrahedron,42, 4451 (1986) etc.
Compound (A) Tetrahedron Letter,33, 5185 (1992) etc.
Compound (B) Journal American Chemical Society,
110, 5917 (1988) etc.
Compound (C) Tetrahedron Letter,34, 4149 (1993) etc.
In the above synthesis method, a compound having a β configuration at the 7-position is usually obtained. However, when a 9-position non-protected taxol derivative is treated with a base at the 9-position, the configuration of the 7-position hydroxyl group is changed from β to α. It is known to isomerize, and if the keto group at the 9-position is reduced to a hydroxyl group after isomerization, a compound having an α-configuration at the 7-position can be synthesized.
[0098]
The compound of the present invention can be used for the treatment of various cancers such as lung cancer, digestive organ cancer, ovarian cancer, uterine cancer, breast cancer, liver cancer, head and neck cancer, blood cancer, renal cancer, testicular tumor and the like.
[0099]
The compound of the present invention can be administered as various injections such as intravenous injection, intramuscular injection and subcutaneous injection, or by various methods such as oral administration and transdermal administration. Among these administration methods, intravenous administration by an aqueous preparation and oral administration are preferable. The aqueous preparation can be prepared by forming an acid adduct with a pharmacologically acceptable acid or by forming an alkali metal salt such as sodium. In the case of oral administration, it may be in the free form or in the salt form.
[0100]
As a preparation method of the preparation, an appropriate preparation can be selected according to the administration method, and it can be prepared by various commonly used preparation methods. Among the dosage forms of the antitumor agent of the present invention, examples of the oral preparation include tablets, powders, granules, capsules, solutions, syrups, elixirs, oily or aqueous suspensions, and the like. In the case of injections, stabilizers, preservatives, solubilizing agents and the like can also be used in the preparation. A solution that may contain these adjuvants and the like may be stored in a container and then used as a solid preparation by freeze-drying or the like.
[0101]
Examples of liquid preparations include solutions, suspensions, emulsions, and the like, but when preparing these preparations, suspensions, emulsifiers, and the like can be used as additives.
[0102]
The compound of the present invention can be used for the treatment of cancer in mammals, particularly humans, and when administered to humans, it is preferably administered once a day and repeated at appropriate intervals.
[0103]
As a dosage, body surface area 1m2It is desirable to administer in the range of about 0.5 mg to 50 mg per dose, preferably about 1 mg to 20 mg.
[0104]
Next, the embodiment will be described in detail.
[0105]
【Example】
Example 1
[0106]
Embedded image
Step 1: 9β-10-deacetyl-9-dihydrobaccatin III
Dissolve 6.98 g of 10-deacetylbaccatin III in a solution of 200 ml of dry methylene chloride and 200 ml of 1,4-dioxane, add 12.89 g of tetrabutylammonium borohydride at room temperature, and leave it at that temperature. Stir for 19 hours. The reaction solution was cooled to 0 ° C., and 1N hydrochloric acid was gradually added dropwise for neutralization. This was concentrated under reduced pressure, and most of the organic solvent was distilled off. Ethyl acetate and water were added and shaken to separate the organic layer, and the aqueous layer was extracted with ethyl acetate. All organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; chloroform: acetone = 5: 1 (v / v)) to obtain 4.794 g of the title compound as a white solid.
[0108]
Rf = 0.65 (chloroform: methanol = 7: 1 (v / v))
FAB Mass: 546 (M+).
[0109]
Step 2: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
0.4825 g of the compound obtained in the above step 1 is dissolved in 4.8 ml of dried methylene chloride and 4.8 ml of 1,4-dioxane, 0.54 ml of 2,2-dimethoxypropane and 19.9 mg of camphorsulfonic acid are added at room temperature, 1 Left for hours. After cooling to 0 ° C., triethylamine was added to adjust pH = 7, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent; chloroform: acetone = 5: 1 (v / v)) to obtain 0.2949 g of the title compound as a white solid.
[0110]
Rf = 0.36 (chloroform: acetone = 6: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.16 (3H, s), 1.41 (3H, s), 1.57 (3H, s), 1.63 (3H, s), 1.64 (3H, s),
1.70-2.20 (4H, m), 3.04 (1H, d, J = 4.9Hz), 3.85 (1H, d, J = 7.3Hz),
4.04 (1H, br-d), 4.33 (1H, d, J = 8.3Hz), 4.39 (1H, d, J = 8.3Hz),
4.67 (1H, d, J = 7.8Hz), 4.80 (1H, br), 5.06 (1H, s), 5.58 (1H, d, J = 7.3Hz),
6.02 (1H, d, J = 4.9Hz), 7.49 (2H, t, J = 7.3Hz), 7.59 (1H, t, J = 7.3Hz),
8.13 (2H, d, J = 7.3Hz).
[0111]
Step 3: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -10-deacetyl-9 -Dihydro-9,10-O-isopropylidenebaccatin III
Dry 49.8 mg of the compound obtained in Step 2 above and 49.0 mg of (3R, 4R) -1- (tert-butoxycarbonyl) -4- (2-furyl) -3- (triisopropylsilyloxy) azetidin-2-one The resulting solution was dissolved in 3.4 ml of tetrahydrofuran, and 1.0 N sodium hexamethyldisilazide (tetrahydrofuran solution) was added dropwise at -58 ° C. After 30 minutes, a saturated aqueous ammonium chloride solution was added at -50 ° C, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (v / v)) to give 15.6 mg of the title compound as a colorless transparent syrup Obtained as material.
[0112]
Rf = 0.09 (hexane: ethyl acetate = 4: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.91-1.02 (22H, m), 1.06 (3H, s), 1.30 (3H, s), 1.39 (9H, s), 1.58 (3H, s),
1.67 (3H, s), 1.68 (3H, s), 1.76 (3H, s), 1.87 (1H, br-s), 2.15-2.23 (2H, m),
2.26-2.39 (2H, m), 2.45 (3H, s), 2.97 (1H, d, J = 4.9Hz), 3.89 (1H, d, J = 7.3Hz),
4.01-4.09 (1H, m), 4.31 (1H, d, J = 8.3Hz), 4.39 (1H, d, J = 8.3Hz),
4.68 (1H, br-d, J = 6.8Hz), 4.99 (1H, s), 5.12 (1H, s), 5.23-5.34 (2H, m),
5.53 (1H, d, J = 7.3Hz), 6.02 (1H, d, J = 4.9Hz), 6.10 (1H, br-t, J = 8.0Hz),
6.25 (1H, d, J = 3.4Hz), 6.34 (1H, dd, J = 3.4Hz, 1.9Hz), 7.37 (1H, d, J = 1.9Hz),
7.48 (2H, t, J = 7.3Hz), 7.59 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
[0113]
Step 4: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-9-dihydro-9, 10-O-isopropylidenebaccatin III
44.3 mg of the compound obtained in the above Step 3 was dissolved in 2.21 ml of dried pyridine, 0.44 ml of hydrogen fluoride-pyridine was added at 0 ° C., and the mixture was returned to room temperature and stirred for 14 hours. Water cooled at 0 ° C. was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine in that order, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: acetone = 6: 1 (v / v)) to give 33.9 mg of the title compound as a colorless transparent syrup-like substance. Got as.
[0114]
Rf = 0.32 (chloroform: acetone = 6: 1 (v / v))
Melting point: 133-135 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.08 (3H, s), 1.28 (3H, s), 1.41 (9H, s), 1.58 (3H, s), 1.65 (3H, s),
1.67 (3H, s), 1.70 (3H, s), 1.83-1.94 (1H, m), 2.07-2.27 (2H, m),
2.36 (3H, s), 2.29-2.47 (1H, m), 2.94 (1H, d, J = 4.9Hz), 3.83 (1H, d, J = 7.3Hz),
4.32 (1H, d, J = 8.7Hz), 4.39 (1H, d, J = 8.7Hz), 4.65-4.76 (2H, m), 5.10 (1H, s),
5.30-5.42 (2H, m), 5.54 (1H, d, J = 7.3Hz), 6.05 (1H, d, J = 4.9Hz),
6.11 (1H, d, J = 3.5Hz), 6.36 (1H, dd, J = 3.5Hz, 1.4Hz), 7.39 (1H, d, J = 1.4Hz),
7.48 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz), 8.11 (2H, d, J = 7.3Hz).
FAB Mass: 840 (MH+).
[0115]
Example 2
[0116]
Embedded image
Step 1: 9β-10-deacetyl-9-dihydro-9,10-O- (4-methoxybenzylidene) baccatin III
The compound obtained in Step 1 of Example 1 was reacted in the same manner as in Step 2 of Example 1 using 4-methoxybenzaldehyde dimethyl acetal in place of 2,2-dimethoxypropane to give the title compound colorless. Obtained as a clear syrupy substance.
[0118]
Rf = 0.24 (chloroform: acetone = 10: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.19 (3H, s), 1.50 (3H, s), 1.61 (3H, s), 1.98 (3H, s), 1.96-2.43 (m),
2.34 (3H, s), 3.10 (1H, d, J = 4.9Hz), 3.84 (3H, s), 3.98 (1H, d, J = 7.3Hz),
4.09-4.19 (1H, m), 4.31 (1H, d, J = 8.3Hz), 4.39 (1H, d, J = 8.3Hz),
4.57 (1H, d, J = 7.8Hz), 4.84 (1H, q, J = 7.2Hz), 5.07 (1H, s),
5.47 (1H, d, J = 7.3Hz), 5.80 (1H, s), 6.04 (1H, d, J = 4.9Hz),
6.93 (2H, d, J = 8.8Hz), 7.42-7.55 (4H, m), 7.60 (1H, t, J = 7.4Hz),
8.12 (2H, d, J = 7.4Hz).
[0119]
Step 2: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -10-deacetyl-9 -Dihydro-9,10-O- (4-methoxybenzylidene) baccatin III
(3R, 4R) -1- (tert-butoxycarbonyl) -4- (2-furyl) -3- (triisopropylsilyl) using the compound obtained in the above step 1 as a raw material in the same manner as in step 3 of Example 1. The title compound was obtained as a colorless and transparent syrupy substance by carrying out a reaction operation with oxy) azetidin-2-one.
[0120]
Rf = 0.28 (hexane: ethyl acetate = 5: 2 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.91-1.08 (21H, m), 1.32 (3H, s), 1.54 (3H, s), 1.72 (3H, s), 1.80 (3H, s),
1.40 (9H, s), 2.17-2.28 (2H, m), 2.36 (2H, d, J = 8.2Hz), 2.47 (3H, s),
3.02 (1H, d, J = 5.0Hz), 3.84 (3H, s), 4.00 (1H, d, J = 7.8Hz), 4.07-4.16 (1H, m),
4.29 (1H, AB type d, J = 8.2Hz), 4.39 (1H, AB type d, J = 8.2Hz),
4.61 (1H, d, J = 7.8Hz), 5.00 (1H, s), 5.12 (1H, s), 5.22-5.36 (2H, m),
5.41 (1H, d, J = 7.8Hz), 5.76 (1H, s), 6.05 (1H, d, J = 5.0Hz),
6.11 (1H, broad t, J = 8.2Hz), 6.26 (1H, d, J = 3.6Hz),
6.34 (1H, dd, J = 3.6Hz, 2.0Hz), 6.93 (2H, d, J = 8.8Hz), 7.38 (1H, d, J = 2.0Hz),
7.43-7.53 (4H, m), 7.59 (1H, t, J = 7.9Hz), 8.02 (2H, d, J = 7.9Hz).
[0121]
Step 3: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-9-dihydro-9, 10-O- (4-Methoxybenzylidene) Baccatin III
The title compound was obtained as a colorless and transparent syrupy substance by performing the same reaction operation as in Step 4 of Example 1 using the compound obtained in Step 2 above as a raw material.
[0122]
Rf = 0.15 (chloroform: acetone = 7: 1 (v / v))
Melting point: 148-151 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (3H, s), 1.42 (9H, s), 1.56 (3H, s), 1.76 (6H, s), 2.10-2.26 (3H, m),
2.36 (3H, s), 2.31-2.48 (1H, m), 2.99 (1H, d, J = 4.9Hz), 3.84 (3H, s),
3.98 (1H, d, J = 7.4Hz), 4.06-4.17 (1H, m), 4.30 (1H, AB type d, J = 8.3Hz),
4.38 (1H, AB type d, J = 8.3Hz), 4.57 (1H, d, J = 8.3Hz), 4.72 (1H, d, J = 3.9Hz),
5.11 (1H, s), 5.38 (2H, broad s), 5.43 (1H, d, J = 7.4Hz), 5.80 (1H, s),
6.07 (1H, d, J = 4.9Hz), 6.15 (1H, broad t, J = 8.0Hz), 6.32 (1H, d, J = 3.8Hz),
6.36 (1H, dd, J = 3.8Hz, 2.0Hz), 6.93 (2H, d, J = 8.8Hz), 7.40 (1H, d, J = 2.0Hz),
7.43-7.53 (4H, m), 7.60 (1H, t, J = 7.3Hz), 8.11 (2H, d, J = 7.3Hz)
FAB mass: 918 (M+).
[0123]
Example 3
[0124]
Embedded image
Step 1: 9β-13-O-allyloxycarbonyl-10-deacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
98.6 mg of the compound obtained in Step 2 of Example 1 was dissolved in 4.0 ml of tetrahydrofuran, and 1.64 N-butyllithium (hexane solution, 0.31 ml) was added dropwise at −78 ° C. After 5 minutes, allyloxycarbonyl chloride 0.025 ml Was added. After 30 minutes, a saturated aqueous ammonium chloride solution was poured at -78 ° C, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 5: 4 (v / v)) to give 52.8 mg of the title compound as a colorless transparent syrup-like substance. Got as.
[0126]
Rf = 0.39 (hexane: ethyl acetate = 5: 4 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23 (3H, s), 1.40 (3H, s), 1.58 (3H, s), 1.64 (3H, s), 1.65 (3H, s),
1.80 (3H, s), 2.11-2.27 (2H, m), 2.26-2.38 (2H, m), 2.31 (3H, s),
2.98 (1H, d, J = 4.8Hz), 3.90 (1H, d, J = 7.8Hz), 4.01-4.09 (1H, m),
4.26 (1H, AB type d, J = 8.3Hz), 4.39 (1H, AB type d, J = 8.3Hz),
4.56 (1H, d, J = 6.8Hz), 4.63-4.76 (2H, m), 5.11 (1H, m), 5.28-5.44 (2H, m),
5.56 (1H, d, J = 7.8Hz), 5.85-6.05 (1H, m), 6.00 (1H, d, J = 4.8Hz),
7.47 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).
[0127]
Step 2: 9β-13-O-allyloxycarbonyl-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
52.8 mg of the compound obtained in the above step 1 was dissolved in 2.2 ml of dry methylene chloride, and 0.036 ml of 2,6-lutidine was added at room temperature. The mixture was cooled to −40 ° C., 0.062 ml of triethylsilyl trifluoromethanesulfonate was added dropwise, and the mixture was stirred for 25 minutes. Saturated sodium hydrogen carbonate solution was added at -40 degreeC, and chloroform extracted. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (v / v)) to give 34.1 mg of the title compound as a colorless transparent syrup-like substance Got as.
[0128]
Rf = 0.32 (hexane: ethyl acetate = 3: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.56-0.71 (6H, m), 1.15 (3H, s), 1.39 (3H, s), 1.47 (3H, s), 1.51 (3H, s),
1.58 (3H, s), 1.81 (3H, s), 2.05-2.15 (1H, m), 2.20-2.34 (2H, m),
2.30 (3H, s), 2.39 (1H, dd, J = 7.6Hz, 14.0Hz), 3.22 (1H, d, J = 5.8Hz),
3.95 (1H, dd, J = 3.4Hz, 9.8HZ), 4.28 (1H, AB type d, J = 7.8Hz),
4.47 (1H, AB type d, J = 7.8Hz), 4.56 (1H, broad d, J = 9.3Hz),
4.68 (2H, d, J = 5.9Hz), 4.82 (1H, t, J = 7.2Hz), 5.27-5.33 (1H, m),
5.34-5.41 (1H, m), 5.43 (1H, d, J = 9.3Hz), 5.82-6.01 (1H, m),
5.86 (1H, d, J = 7.8Hz), 5.88 (1H, t, J = 7.6Hz), 7.47 (2H, t, J = 7.8Hz),
7.58 (1H, t, J = 7.8Hz), 8.09 (2H, d, J = 7.8Hz).
[0129]
Step 3: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
32.1 mg of the compound obtained in the above step 2 was dissolved in 1.0 ml of tetrahydrofuran, 0.005 ml of methanol and 4.3 mg of tetrakistriphenylphosphine palladium were added at room temperature, and the mixture was stirred for 1 hour in a nitrogen atmosphere. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 5: 3 (v / v)) to give 17.1 mg of the title compound as a colorless transparent syrup. Obtained as material.
[0130]
Rf = 0.29 (hexane: ethyl acetate = 5: 3 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.61 (6H, q, J = 7.8Hz), 0.96 (9H, t, J = 7.8Hz), 1.11 (3H, s), 1.40 (3H, s),
1.50 (3H, s), 1.57 (3H, s), 1.59 (3H, s), 1.93 (3H, s), 1.88-2.15 (2H, m),
2.23-2.47 (2H, m), 2.32 (3H, s), 3.16 (1H, d, J = 5.3Hz), 4.17 (1H, t, J = 4.8Hz),
4.17-4.29 (1H, m), 4.20 (1H, AB type d, J = 7.8Hz),
4.29 (1H, AB type d, J = 7.8Hz), 4.73-4.88 (2H, m), 5.51 (1H, d, J = 7.8Hz),
5.91 (1H, d, J = 5.3Hz), 7.48 (2H, t, J = 7.3Hz), 7.59 (1H, t, J = 7.3Hz),
8.14 (2H, d, J = 7.3Hz).
[0131]
Step 4: 9β-13-O- [3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3- (4-pyridyl) propionyl] -10-deacetyl-9-dihydro-9 , 10-O-isopropylidene-7-O-triethylsilylbaccatin III
The compound obtained in the above step 3 was used as a raw material, and cis-1- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyloxy) -4- (4-pyridyl) was used in the same manner as in step 3 of Example 1. By carrying out the reaction with azetidin-2-one, the title compound, which is a mixture of two diastereoisomers in which the relative configuration at the 2′-position and the 3′-position is threo (syn), is colorless and transparent. Obtained as a syrupy substance.
[0132]
Rf = 0.32 (hexane: ethyl acetate = 5: 4 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.30-0.37 (m), 0.60-1.02 (m), 1.25-1.88 (m), 2.10-2.58 (m),
2.24 and 2.54 (total 3H, each s),
3.10 and 3.15 (total 1H, each d, J = 5.4Hz and J = 5.9Hz), 3.92-4.18 (m),
4.21-4.60 (m), 4.84 and 4.94 (total 1H, each t, J = 6.3Hz and J = 4.8Hz),
5.21-5.68 (m), 5.88 and 5.94 (total 1H, each d, J = 5.9Hz and J = 5.4Hz),
6.18-6.30 (m), 7.18-7.64 (m), 8.11 (2H, d, J = 7.3Hz), 8.52-8.70 (m).
[0133]
Step 5: 9β-13-O- [3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -10-deacetyl-9-dihydro-9,10-O-isopropylidene Baccatin III
27.1 mg of the compound obtained in the above Step 4 was dissolved in 1.35 ml of pyridine, 0.27 ml of hydrogen fluoride pyridine was added dropwise at 0 ° C., and the mixture was stirred at room temperature for 6 hours. Water cooled at 0 ° C. was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (chloroform: methanol = 12: 1 (v / v)), and the relative stereochemistry at the 2 ′ and 3 ′ positions in the title compound was obtained. Of the two diastereoisomers having a threo (syn) configuration, the low polar isomer A and the high polar isomer B were each obtained as a colorless and transparent syrup-like substance.
[0134]
Isomer A
Rf = 0.27 (chloroform: methanol = 12: 1 (v / v))
Melting point: 157-159 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.40 (3H, s), 1.51 (3H, s), 1.58 (3H, s), 1.63 (3H, s),
1.66 (3H, s), 1.42 (9H, s), 1.92 (1H, broad s), 1.96-2.02 (2H, m),
2.16-2.41 (2H, m), 2.30 (3H, s), 2.89 (1H, d, J = 4.4Hz), 3.77 (1H, d, J = 7.4Hz),
4.03-4.12 (1H, m), 4.35 (1H, AB type d, J = 8.8Hz),
4.38 (1H, AB type d, J = 8.8Hz), 4.63 (1H, s), 4.68 (1H, d, J = 8.3Hz),
5.11 (1H, s d), 5.30 (1H, broad d, J = 9.8Hz), 5.52 (1H, broad d, J = 7.4Hz),
5.74 (1H, broad d, J = 9.8Hz), 6.06 (1H, d, J = 4.4Hz), 6.10 (1H, t, J = 7.8Hz),
7.35 (2H, d, J = 5.9Hz), 7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.10 (2H, d, J = 7.8Hz), 8.59 (2H, d, J = 5.9Hz)
FAB mass: 851 (MH+).
[0135]
Isomer B
Rf = 0.25 (chloroform: methanol = 12: 1 (v / v))
Melting point: 160-163 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.29 (3H, s), 1.40 (3H, s), 1.59 (3H, s), 1.63 (3H, s), 1.68 (3H, s),
1.81 (3H, s), 1.40 (9H, s), 1.92 (1H, broad s), 2.05-2.42 (4H, m),
2.19 (3H, s), 2.93 (1H, d, J = 4.9Hz), 3.83 (1H, d, J = 7.3Hz), 4.03-4.13 (1H, m),
4.32 (1H, AB type d, J = 8.3Hz), 4.39 (1H, AB type d, J = 8.3Hz),
4.51 (1H, broad s), 4.73 (1H, d, J = 7.3Hz), 5.18 (1H, s like),
5.30 (1H, broad d, J = 8.4Hz), 5.46-5.61 (2H, m), 6.06 (1H, d, J = 4.9Hz),
6.23 (1H, m), 7.42 (2H, d, J = 6.8Hz), 7.46 (2H, t, J = 7.6Hz),
7.60 (1H, t, J = 7.6Hz), 8.10 (2H, d, J = 7.6Hz), 8.62 (2H, d, J = 6.8Hz)
FAB mass: 851 (MH+).
[0136]
Example 4
[0137]
Embedded image
Step 1: 9β-10-deacetyl-9-dihydro-9,10-O- (2-propenylidene) baccatin III
By using the compound obtained in Step 1 of Example 1 as a raw material and using acrolein diethyl acetal instead of 2,2-dimethoxypropane, the same reaction operation as in Step 2 of Example 1 was carried out, whereby the title compound was obtained. Obtained.
[0139]
Rf = 0.30 (chloroform: acetone = 5: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.17 (3H, s), 1.62 (3H, s), 1.65 (3H, s), 1.92 (3H, s), 1.82 (1H, s),
1.98 (1H, dd, J = 16.0Hz, 6.8Hz), 2.09-2.42 (3H, m), 2.34 (3H, s),
3.05 (1H, d, J = 4.4Hz), 3.89 (1H, d, J = 6.8Hz), 4.06-4.16 (1H, m),
4.32 (1H, AB type d, J = 8.3Hz), 4.40 (1H, AB type d, J = 8.3Hz),
4.59 (1H, d, J = 7.8Hz), 4.82 (1H, broad q, J = 6.8Hz), 5.07 (1H, s),
5.22 (1H, d, J = 6.3Hz), 5.30 (1H, d, J = 6.8Hz), 5.45 (1H, d, J = 10.3Hz),
5.56 (1H, d, J = 17.6Hz), 6.04 (1H, d, J = 4.4Hz), 5.96-6.11 (1H, m),
7.48 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz), 8.13 (2H, d, J = 7.3Hz).
[0140]
Step 2: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -10-deacetyl-9 -Dihydro-9,10-O- (2-propenylidene) baccatin III
The title compound was obtained by carrying out the same reaction operation as in step 3 of Example 1 using the compound obtained in the above step 1 as a raw material.
[0141]
Rf = 0.16 (chloroform: acetone = 12: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.91-1.03 (21H, m), 1.30 (3H, s), 1.64 (3H, s), 1.68 (3H, s), 1.75 (3H, s),
1.40 (9H, s), 1.89 (1H, s), 2.21 (2H, m), 2.33 (2H, d, J = 8.8Hz), 2.46 (3H, s),
2.96 (1H, d, J = 4.9Hz), 3.91 (1H, d, J = 6.9Hz), 4.05-4.14 (1H, m),
4.30 (1H, AB type d, J = 8.3Hz), 4.40 (1H, AB type d, J = 8.3Hz),
4.63 (1H, d, J = 8.3Hz), 5.00 (1H, s), 5.12 (1H, s), 5.19 (1H, d, J = 6.4Hz),
5.24 (1H, d, J = 6.9Hz), 5.22-5.34 (2H, m), 5.45 (1H, d, J = 10.3Hz),
5.57 (1H, d, J = 17.5Hz), 5.94-6.15 (2H, m), 6.05 (1H, d, J = 4.9Hz),
6.25 (1H, d, J = 2.9Hz), 6.34 (1H, dd, J = 2.9Hz, 1.9Hz), 7.37 (1H, d, J = 1.9Hz),
7.47 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz).
[0142]
Step 3: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-9-dihydro-9, 10-O- (2-propenylidene) baccatin III
The title compound was obtained as a colorless and transparent syrupy substance by performing the same reaction operation as in Step 4 of Example 1 using the compound obtained in Step 2 above as a raw material.
[0143]
Rf = 0.05 (chloroform: acetone = 12: 1 (v / v))
Melting point: 147-150 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.28 (3H, s), 1.62 (3H, s), 1.69 (3H, s), 1.71 (3H, s), 1.41 (9H, s),
2.05-2.26 (3H, m), 2.29-2.44 (1H, m), 2.35 (3H, s), 2.93 (1H, d, J = 4.9Hz),
3.89 (1H, d, J = 6.8Hz), 4.04-4.16 (1H, m), 4.32 (1H, AB type d, J = 8.3Hz),
4.39 (1H, AB type d, J = 8.3Hz), 4.71 (1H, s), 5.10 (1H, s),
5.22 (1H, d, J = 5.9Hz), 5.27 (1H, d, J = 6.8Hz), 5.32-5.46 (2H, m),
5.46 (1H, d, J = 10.8Hz), 5.57 (1H, d, J = 17.6Hz), 5.97-6.19 (2H, m),
6.08 (1H, d, J = 4.9Hz), 6.32 (1H, d, J = 1.9Hz), 6.36 (1H, dd, J = 3.0Hz, 1.9Hz),
7.39 (1H, d, J = 3.0Hz), 7.48 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.10 (2H, d, J = 7.8Hz)
FAB mass: 838 (MH+).
[0144]
Example 5
[0145]
Embedded image
Step 1: 9β-7-O-allyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -10-deacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
34.4 mg of the compound obtained in Step 3 of Example 1 was dissolved in 1.4 ml of tetrahydrofuran, 1N sodium hexamethyldisilazide (tetrahydrofuran solution, 0.14 ml) was added dropwise at −50 ° C., and after 5 minutes, allyl iodide 0.020 ml was added at the same temperature and stirred for 1.5 hours, and 0.020 ml of allyl iodide was added again at -42 ° C, followed by stirring for 1.5 hours. Saturated aqueous ammonium chloride solution was poured at −40 ° C., and the mixture was extracted with ethyl acetate. After washing with saturated brine and drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 5: 1 (v / v) ) To obtain 2.6 mg of the title compound in which the hydroxyl group at the 7-position was etherified from Rf = 0.12 as a colorless transparent syrup-like substance. Further, 4.2 mg of a compound in which the acetyl group at the 4-position was allylated from Rf = 0.27 was obtained.
[0147]
Rf = 0.12 (Hexane: Ethyl acetate = 6: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.90-1.02 (m), 1.22 (3H, s), 1.36 (3H, s), 1.38 (9H, s), 1.51 (3H, s),
1.53 (3H, s), 1.57 (3H, s), 1.77 (3H, s), 2.02-2.48 (4H, m), 2.44 (3H, s),
3.23 (1H, d, J = 5.8Hz), 3.45 (1H, dd, J = 2.9Hz, 9.8Hz),
3.84 (1H, dd, J = 12.7Hz, 5.4Hz), 4.17 (1H, dd, J = 12.7Hz, 5.4Hz),
4.26 (1H, AB type d, J = 7.8Hz), 4.56 (1H, AB type d, J = 7.8Hz),
4.32 (1H, d, J = 8.8Hz), 4.82 (1H, t, J = 6.4Hz), 4.96 (1H, s),
5.14 (1H, dd, J = 10.3Hz, 1.0Hz), 5.21-5.36 (2H, m), 5.42 (1H, d, J = 8.8Hz),
5.87 (1H, d, J = 5.8Hz), 5.82-5.98 (1H, m), 6.14 (1H, broad t, J = 8.4Hz),
6.24 (1H, d, J = 2.9Hz), 6.34 (1H, dd, J = 2.9Hz, 1.0Hz), 7.37 (1H, d, J = 1.0Hz),
7.47 (2H, t, J = 7.8Hz), 7.56 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
[0148]
Step 2: 9β-7-O-allyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl- 9-Dihydro-9,10-O-isopropylidenebaccatin III
The title compound was obtained as a colorless and transparent syrupy substance by performing the same reaction operation as in Step 4 of Example 1 using the compound obtained in Step 1 above as a raw material.
[0149]
Rf = 0.68 (chloroform: acetone = 12: 1 (v / v))
Melting point: 112-115 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23 (3H, s), 1.25 (3H, s), 1.39 (3H, s), 1.40 (9H, s), 1.46-1.61 (6H, m),
1.73 (3H, s), 1.68-1.82 (1H, m), 2.08-2.40 (3H, m), 2.35 (3H, s),
3.12 (1H, d, J = 3.9Hz), 3.44-3.56 (1H, m), 3.83 (1H, dd, J = 13.0Hz, 6.0Hz),
4.17 (1H, dd, J = 13.0Hz, 4.8Hz), 4.23 (1H, d, J = 7.8Hz), 4.56 (1H, d, J = 8.3Hz),
4.70 (1H, d, J = 3.5Hz), 4.83 (1H, t, J = 4.9Hz), 5.12 (1H, d, J = 8.8Hz),
5.27 (1H, d, J = 16.1Hz), 5.35 (1H, broad s), 5.46 (1H, d, J = 8.3Hz),
5.82-5.98 (1H, m), 5.92 (1H, d, J = 3.9Hz), 6.14 (1H, broad t, J = 8.4Hz),
6.31 (1H, d, J = 2.9Hz), 6.37 (1H, dd, J = 2.9Hz, 1.5Hz), 7.40 (1H, d, J = 1.5Hz),
7.47 (2H, t, J = 7.8Hz), 7.58 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).
FAB Mass: 880 (M+).
[0150]
Example 6
[0151]
Embedded image
Step 1: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -4,10-dideacetyl -9-Dihydro-9,10-O-isopropylidene-4-O- (4-pentenoyl) baccatin III
By the operation in Step 1 of Example 5, 4.2 mg of the title compound in which the acetyl group at the 4-position was allylated from Rf = 0.27 was obtained.
[0153]
Rf = 0.27 (hexane: ethyl acetate = 6: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.91-1.04 (m), 1.23 (3H, s), 1.36 (3H, s), 1.37 (9H, s), 1.47 (3H, s),
1.50-1.60 (6H, m), 1.76 (3H, s), 2.09 (1H, ddd, J = 5.2Hz, 8.8Hz, 14.4Hz),
2.15-2.31 (2H, m), 2.40 (1H, dd, J = 8.8Hz, 15.2Hz), 2.53-2.64 (2H, m),
2.71 (1H, q, J = 7.6Hz), 2.87 (1H, q, J = 7.6Hz), 3.18 (1H, d, J = 5.4Hz),
3.92 (1H, dd, J = 8.8Hz, 3.4Hz), 4.26 (1H, AB type d, J = 8.3Hz),
4.51 (1H, AB type d, J = 8.3Hz), 4.41 (1H, broad d, J = 8.3Hz),
4.76 (1H, t, J = 6.4Hz), 4.96 (1H, s), 5.03 (1H, q, J = 10.8Hz),
5.14 (1H, dd, J = 17.1Hz, 1.0Hz), 5.21-5.33 (2H, m), 5.40 (1H, d, J = 8.3Hz),
5.81-5.97 (1H, m), 5.89 (1H, d, J = 5.4Hz), 6.10 (1H, t, J = 8.8Hz),
6.25 (1H, d, J = 3.4Hz), 6.35 (1H, dd, J = 3.4Hz, 2.8Hz), 7.36 (1H, d, J = 2.8Hz),
7.48 (2H, t, J = 7.3Hz), 7.57 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
[0154]
Step 2: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl-9-dihydro- 9,10-O-isopropylidene-4-O- (4-pentenoyl) baccatin III
The title compound was obtained by carrying out the reaction procedure of Step 4 of Example 1 using the compound obtained in the above Step 1 as a raw material.
[0155]
Rf = 0.20 (chloroform: acetone = 10: 1 (v / v))
Melting point: 105-110 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.28 (3H, s), 1.40 (9H, s), 1.58 (3H, s), 1.64 (3H, s),
1.67 (3H, s), 1.70 (3H, s), 2.07-2.28 (3H, m), 2.30-2.41 (1H, m),
2.49-2.66 (3H, m), 2.69-2.80 (1H, m), 2.94 (1H, d, J = 4.4Hz),
3.66 (1H, broad s), 3.84 (1H, d, J = 5.4Hz), 4.06 (1H, m),
4.33 (1H, AB type d, J = 8.3Hz), 4.38 (1H, AB type d, J = 8.3Hz),
4.64-4.73 (2H, m), 4.99-5.10 (2H, m), 5.13 (1H, dd, J = 1.0Hz, 17.0Hz),
5.31 (1H, s), 5.54 (1H, d, J = 8.3Hz), 5.75-5.89 (1H, m), 6.05 (1H, d, J = 4.4Hz),
6.10 (1H, broad t, J = 7.2Hz), 6.32 (1H, d, J = 3.4Hz),
6.36 (1H, dd, J = 3.4Hz, 1.5Hz), 7.39 (1H, d, J = 1.5Hz), 7.48 (2H, t, J = 7.4Hz),
7.61 (1H, t, J = 7.4Hz), 8.13 (2H, d, J = 7.4Hz).
FAB Mass: 880 (M+).
[0156]
Example 7
[0157]
Embedded image
Step 1: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-9-dihydro -9,10-O- (2-propenylidene) baccatin III
(3R, 4S) -1- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyloxy) was prepared in the same manner as in Step 3 of Example 1, using the compound obtained in Step 1 of Example 4 as a starting material. Reaction with -4-phenylazetidin-2-one gave the title compound as a clear, colorless syrup.
[0159]
Rf = 0.35 (chloroform: acetone = 7: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.33 (3H, s), -0.11 (3H, s), 0.74 (9H, s), 1.33 (3H, s), 1.38 (9H, s),
1.64 (3H, s), 1.69 (3H, s), 1.73 (3H, s), 1.85 (1H, s), 2.13-2.28 (3H, m),
2.33 (1H, dd, J = 9.3Hz, 14.6Hz), 2.53 (3H, s), 2.96 (1H, d, J = 4.9Hz),
3.91 (1H, d, J = 7.3Hz), 4.04-4.14 (1H, m), 4.33 (1H, AB type d, J = 8.3Hz),
4.40 (1H, AB type d, J = 8.3Hz), 4.53 (1H, s), 4.59 (1H, d, J = 7.8Hz),
5.13 (1H, s), 5.19 (1H, d, J = 5.9Hz), 5.23 (1H, d, J = 7.3Hz),
5.30 (1H, broad d, J = 8.8Hz), 5.45 (1H, d, J = 10.3Hz), 5.57 (1H, d, J = 17.6Hz),
5.96-6.10 (1H, m), 6.04 (1H, d, J = 4.9Hz), 6.20 (1H, t, J = 8.8Hz),
7.18-7.41 (5H, m), 7.48 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.13 (2H, d, J = 7.8Hz).
[0160]
Step 2: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O— (2-propenylidene) baccatin III
The title compound was obtained by carrying out the same reaction operation as in step 4 of Example 1 using the compound obtained in the above step 1.
[0161]
Rf = 0.30 (chloroform: acetone = 5: 1 (v / v))
Melting point: 145-150 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.40 (9H, s), 1.61 (6H, s), 1.68 (3H, s), 1.91 (1H, s),
2.00-2.36 (3H, m), 2.30 (3H, s), 2.39 (1H, dd, J = 9.8Hz, 15.2Hz),
2.90 (1H, d, J = 4.9Hz), 3.85 (1H, d, J = 6.8Hz), 4.06-4.15 (1H, m),
4.16 (1H, broad s), 4.32 (1H, AB type d, J = 8.8Hz),
4.38 (1H, AB type d, J = 8.8Hz), 4.57 (1H, d, J = 8.3Hz), 4.62 (1H, broad s),
5.10 (1H, s), 5.22 (1H, d, J = 6.3Hz), 5.26 (1H, d, J = 6.8Hz),
5.30 (1H, broad d, J = 9.7Hz), 5.97-6.13 (2H, m), 6.07 (1H, d, J = 4.3Hz),
7.20-7.45 (5H, m), 7.47 (2H, t, J = 7.4Hz), 7.60 (1H, t, J = 7.4Hz),
8.10 (2H, d, J = 7.4Hz).
FAB Mass: 848 (MH+).
[0162]
Example 8
[0163]
Embedded image
Step 1: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-9-dihydro-9, 10-O- (2,3-dihydroxypropylidene) baccatin III
35.1 mg of the compound obtained in Step 3 of Example 4 was dissolved in 1.1 ml of tetrahydrofuran and 0.35 ml of distilled water, and 26.8 mg of N-morpholine-N-oxide and 4.8 mg of osmium tetroxide were added at room temperature. After 21 hours, an aqueous sodium sulfite solution was added, and the mixture was extracted with ethyl acetate. After washing with saturated brine and drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: methanol = 10: 1 (v / v)). Thus, 14.1 mg of the title compound was obtained as a colorless transparent syrupy substance.
[0165]
Rf = 0.25 (chloroform: methanol = 8: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.29 (3H, s), 1.41 (9H, s), 1.63 (3H, s), 1.69 (3H, s),
1.70 (3H, s), 2.00-2.55 (m), 2.36 (3H, s), 2.93 (1H, d, J = 4.9Hz),
3.70-4.00 (m), 4.05-4.18 (1H, m), 4.30 (1H, AB type d, J = 8.8Hz),
4.38 (1H, AB type d, J = 8.8Hz), 4.71 (1H, s), 4.75-4.92 (2H, m), 5.10 (1H, s),
5.26 (1H, d, J = 4.9Hz), 5.35 (1H, broad d, J = 9.7Hz), 6.03 (1H, d, J = 7.3Hz),
6.08-6.16 (1H, m), 6.31 (1H, d, J = 3.4Hz), 6.36 (1H, dd, J = 3.4Hz, 1.5Hz),
7.39 (1H, d, J = 1.5Hz), 7.42-7.67 (3H, m), 8.02-8.17 (2H, m).
[0166]
Step 2: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-9-dihydro-9, 10-O- (2-morpholinoethylidene) baccatin III
14.1 mg of the compound obtained in the above step 1 is dissolved in a mixed solvent of tetrahydrofuran-water-methanol (1: 1: 1 (v / v)), 19.7 mg of sodium metaperiodate is added at room temperature, and the mixture is stirred for 30 minutes. did. The mixture was cooled to 0 ° C., brine was added, and the mixture was extracted with ethyl acetate. After washing with saturated brine and drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was vacuum dried. This was dissolved in ethanol 1.3 ml, acetic acid 0.10 ml, morpholine 0.14 ml, sodium cyanoborohydride 13.9 mg were added at room temperature, and the mixture was stirred for 1 hour. Saturated aqueous sodium hydrogen carbonate and saturated brine were added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (chloroform: methanol = 12: 1 (v / v)) to give 10.4 mg of the title compound as colorless. Obtained as a clear syrupy substance.
[0167]
Rf = 0.56 (chloroform: methanol = 10: 1 (v / v))
Melting point; 149-152 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.41 (9H, s), 1.60 (3H, s), 1.65 (3H, s), 1.69 (3H, s),
1.89 (1H, s), 2.08-2.26 (3H, m), 2.35 (3H, s), 2.31-2.43 (1H, m),
2.54-2.70 (4H, m), 2.74 (1H, dd, J = 5.4Hz, 13.7Hz),
2.82 (1H, dd, J = 3.9Hz, 13.7Hz), 2.92 (1H, d, J = 4.7Hz), 3.69-3.79 (4H, m),
3.80 (1H, d, J = 6.9Hz), 3.87-3.94 (1H, broad), 4.04-4.11 (1H, m),
4.31 (1H, AB type d, J = 8.3Hz), 4.39 (1H, AB type d, J = 8.3Hz),
4.67 (1H, d, J = 8.3Hz), 4.71 (1H, s), 5.02 (1H, dd, J = 5.4Hz, 3.9Hz),
5.11 (1H, s), 5.20 (1H, d, J = 6.9Hz), 5.30-5.42 (2H, m), 6.04 (1H, d, J = 4.7Hz),
6.11 (1H, broad t, J = 8.0Hz), 6.31 (1H, d, J = 3.4Hz),
6.36 (1H, dd, J = 3.4Hz, 2.0Hz), 7.39 (1H, d, J = 2.0Hz), 7.48 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).
FAB Mass: 911 (M+).
[0168]
Example 9
[0169]
Embedded image
Step 1: 9β-10-deacetyl-9-dihydro-9,10-O- (2-propenylidene) -7-O- (2,2,2-trichloroethoxycarbonyl) baccatin III
100.4 mg of the compound obtained in Step 1 of Example 4 was dissolved in 3.0 ml of pyridine, and 0.025 ml of 2,2,2-trichloroethoxycarbonyl chloride was added dropwise at 0 ° C. After 30 minutes, water cooled at 0 ° C. was added, extracted with ethyl acetate, and washed successively with 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate, and saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform: acetone = 6: 1 (v / v)) to give 116.7 mg of the title compound as colorless and transparent Obtained as a syrupy substance.
[0171]
Rf = 0.48 (chloroform: acetone = 5: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.16 (3H, s), 1.60 (3H, s), 1.62 (3H, s), 1.96 (3H, s), 1.80 (1H, s),
1.91-2.00 (1H, m), 2.20 (1H, dt, J = 16.0Hz, 4.4Hz), 2.29-2.43 (2H, m),
2.35 (3H, s), 3.20 (1H, d, J = 4.9Hz), 3.97 (1H, d, J = 7.3Hz),
4.31 (1H, AB type d, J = 8.3Hz), 4.44 (1H, AB type d, J = 8.3Hz),
4.66 (1H, AB type d, J = 11.7Hz), 4.83 (1H, AB type d, J = 11.7Hz),
4.76-4.89 (2H, m), 5.15 (1H, dd, J = 5.3Hz, 3.4Hz), 5.19 (1H, d, J = 5.9Hz),
5.34 (1H, d, J = 7.3Hz), 5.46 (1H, d, J = 10.3Hz), 5.57 (1H, d, J = 17.5Hz),
5.98 (1H, d, J = 4.9Hz), 6.04 (1H, ddd, J = 17.5Hz, 10.3Hz, 5.9Hz),
7.48 (2H, t, J = 7.4Hz), 7.59 (1H, t, J = 7.4Hz), 8.13 (2H, d, J = 7.4Hz).
[0172]
Step 2: 9β-13-O- [3- (tert-butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionyl] -10-deacetyl-9-dihydro-9,10-O— (2-propenylidene) -7-O- (2,2,2-trichloroethoxycarbonyl) baccatin III
0.2041 g of 3- (tert-butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionic acid was dissolved in 4.0 ml of toluene, and 0.1516 g of di-2-pyridyl carbonate was added at room temperature. After 20 minutes, a suspension of the compound obtained in Step 1 (0.1167 g) in toluene (2.0 ml) was added, 4-dimethylaminopyridine (39.9 mg) was added, and the mixture was heated to 65 ° C. and stirred for 16 hours. The mixture was allowed to cool to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; chloroform: acetone = 20: 1 (v / v)) to give the title compound 75.5 mg Was obtained as a colorless transparent syrupy substance.
[0173]
Rf = 0.44 (chloroform: acetone = 20: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.28 (3H, s), 1.43 (9H, s), 1.47 (3H, s), 1.62 (3H, s), 1.64 (3H, s),
1.90 (1H, broad s), 2.19-2.40 (6H, m), 3.13 (1H, d, J = 4.7Hz),
3.95-4.01 (1H, m), 4.31 (1H, AB type d, J = 8.3Hz),
4.39 (1H, AB type d, J = 8.3Hz), 4.67 (1H, AB type d, J = 11.7Hz),
4.85 (1H, AB type d, J = 11.7Hz), 4.87-4.94 (1H, m), 5.08-5.17 (2H, m),
5.28 (1H, t, J = 8.3Hz), 5.38 (1H, broad d, J = 8.8Hz), 5.46 (1H, d, J = 10.2Hz),
5.56 (1H, d, J = 17.5Hz), 5.58-5.73 (1H, m), 5.96 (1H, d, J = 4.7Hz),
6.04 (1H, ddd, J = 17.5Hz, 10.2Hz, 5.9Hz), 6.12-6.28 (1H, m),
6.31-6.46 (2H, m), 7.38-7.51 (3H, m), 7.60 (1H, t, J = 7.4Hz),
8.06-8.14 (2H, m).
[0174]
Step 3: 9β-13-O- [3- (tert-butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionyl] -10-deacetyl-9-dihydro-9,10-O— (2-propenylidene) baccatin III
75.5 mg of the compound obtained in Step 2 above was dissolved in 6.0 ml of a mixed solvent of acetic acid-methanol (1: 1 (v / v)), 0.1728 g of zinc powder was added at room temperature, and the mixture was stirred at 62 ° C. for 30 minutes. The solid was filtered and the filtrate was concentrated under reduced pressure. This was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate and saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (chloroform: acetone = 7: 1 (v / v)) to give 14.7 mg of the title compound colorless. Obtained as a clear syrupy substance.
[0175]
Rf = 0.30 (chloroform: acetone = 8: 1 (v / v))
Melting point: 124-127 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (3H, s), 1.43 (9H, s), 1.62 (6H, s), 1.89 (1H, s), 2.16-2.35 (4H, m),
2.26 (3H, s), 2.92 (1H, d, J = 4.9Hz), 3.83-3.94 (1H, m), 4.04-4.10 (1H, m),
4.28 (1H, AB type d, J = 8.3Hz), 4.40 (1H, AB type d, J = 8.3Hz),
4.60 (1H, broad d, J = 8.3Hz), 5.12 (1H, s), 5.17-5.28 (2H, m),
5.31-5.41 (1H, m), 5.45 (1H, d, J = 10.7Hz), 5.56 (1H, d, J = 17.6Hz),
5.55-5.72 (1H, m), 5.94-6.07 (1H, m), 6.03 (1H, d, J = 4.9Hz),
6.12-6.25 (1H, m), 6.35-6.46 (2H, m), 7.42 (1H, s), 7.48 (2H, t, J = 7.3Hz),
7.60 (1H, t, J = 7.3Hz), 8.06-8.14 (2H, m).
FAB Mass: 858 (M+).
[0176]
Example 10
[0177]
Embedded image
Step 1: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O- (2,2,2-trichloroethoxycarbonyl) baccatin III
The title compound was obtained as a colorless and transparent syrupy substance by performing the same reaction operation as in Step 1 of Example 9 using the compound obtained in Step 2 of Example 1 as a raw material.
[0179]
Rf = 0.33 (chloroform: acetone = 7: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.16 (3H, s), 1.41 (3H, s), 1.56 (3H, s), 1.58 (3H, s), 1.59 (3H, s),
1.79 (1H, s), 1.89-2.01 (1H, m), 1.95 (3H, s), 2.04-2.13 (1H, m),
2.27-2.49 (2H, m), 2.35 (3H, s), 3.20 (1H, d, J = 4.9Hz), 3.96 (1H, d, J = 7.3Hz),
4.28 (1H, AB type d, J = 7.8Hz), 4.51 (1H, AB type d, J = 7.8Hz),
4.65 (1H, AB type d, J = 11.7Hz), 4.80 (1H, AB type d, J = 11.7Hz),
4.75-4.86 (2H, m), 5.08-5.13 (1H, m), 5.60 (1H, d, J = 7.3Hz),
5.96 (1H, d, J = 4.9Hz), 7.48 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz),
8.15 (2H, d, J = 7.3Hz).
[0180]
Step 2: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O- (2,2,2-trichloroethoxycarbonyl) -13-O-triethylsilylbaccatin III
The title compound was obtained as colorless and transparent crystals by carrying out the same reaction operation as in Step 2 of Example 3 using the compound obtained in Step 1 as a raw material.
[0181]
Rf = 0.45 (hexane: ethyl acetate = 3: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.55-0.71 (6H, m), 1.01 (9H, t, J = 7.8Hz), 1.20 (3H, s), 1.36 (3H, s),
1.52 (3H, s), 1.55 (3H, s), 1.58 (3H, s), 1.74 (1H, s), 1.88 (3H, s),
2.10 (1H, dd, J = 14.4Hz, 8.8Hz), 2.16-2.42 (3H, m), 2.28 (3H, s),
3.19 (1H, d, J = 5.4Hz), 4.10 (1H, d, J = 8.3Hz), 4.30 (1H, AB type d, J = 7.8Hz),
4.47 (1H, AB type d, J = 7.8Hz), 4.67 (1H, AB type d, J = 11.7Hz),
4.81 (1H, AB type d, J = 11.7Hz), 4.90 (1H, t, J = 5.3Hz), 4.96 (1H, t, J = 8.8Hz),
5.04 (1H, dd, J = 7.9Hz, 3.0Hz), 5.49 (1H, d, J = 8.3Hz), 5.84 (1H, d, J = 5.4Hz),
7.47 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).
[0182]
Step 3: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-13-O-triethylsilylbaccatin III
The title compound was obtained as a white foamy substance by carrying out the same reaction operation as in step 3 of Example 9 using the compound obtained in the above step 2.
[0183]
Rf = 0.27 (hexane: ethyl acetate = 3: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.58-0.75 (6H, m), 1.01 (9H, t, J = 7.8Hz), 1.24 (3H, s), 1.40 (3H, s),
1.56 (3H, s), 1.62 (6H, s), 1.80 (1H, s), 1.86 (3H, s), 2.03-2.31 (4H, m),
2.27 (3H, s), 2.94 (1H, d, J = 4.9Hz), 3.95 (1H, d, J = 7.9Hz), 3.99-4.07 (1H, m),
4.28 (1H, AB type d, J = 8.3Hz), 4.38 (1H, AB type d, J = 8.3Hz),
4.61 (1H, d, J = 7.3Hz), 4.97 (1H, t, J = 8.8Hz), 5.10 (1H, t, J = 3.4Hz),
5.52 (1H, d, J = 7.9Hz), 5.95 (1H, d, J = 4.9Hz), 7.47 (2H, t, J = 7.8Hz),
7.59 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz).
[0184]
Step 4: 9β-7-O-allyl-10-deacetyl-9-dihydro-9,10-O-isopropylidene-13-O-triethylsilylbaccatin III
Dissolve 0.2400 g of the compound obtained in Step 3 above in 7.2 ml of dry tetrahydrofuran, add dropwise 1.64 N butyllithium (hexane solution, 0.315 ml) at -50 ° C, and 17 minutes later, allyl iodide (0.15 ml) in dimethyl Sulfoxide (1.80 ml) solution was added and stirred at 0 ° C. for 1.5 hours. A saturated aqueous ammonium chloride solution was added at 0 ° C., and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 10: 3 (v / v)) to obtain 0.1358 g of the title compound as a white solid.
[0185]
Rf = 0.41 (hexane: ethyl acetate = 3: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.59-0.74 (6H, m), 1.01 (9H, t, J = 7.8Hz), 1.37 (3H, s), 1.43 (3H, s),
1.50 (3H, s), 1.57 (3H, s), 1.65 (1H, s), 1.87 (3H, s), 2.00-2.14 (2H, m),
2.21-2.47 (2H, m), 2.28 (3H, s), 3.26 (1H, d, J = 5.8Hz),
3.42 (1H, dd, J = 11.7Hz, 3.4Hz), 3.85 (1H, dd, J = 12.7Hz, 5.4Hz),
4.18 (1H, dd, J = 12.7Hz, 5.4Hz), 4.29 (1H, AB type d, J = 7.8Hz),
4.54 (1H, AB type d, J = 7.8Hz), 4.40 (1H, d, J = 9.8Hz), 4.82 (1H, t, J = 8.3Hz),
4.93 (1H, t, J = 8.3Hz), 5.16 (1H, dd, J = 10.3Hz, 1.5Hz),
5.32 (1H, dd, J = 17.1Hz, 1.5Hz), 5.41 (1H, d, J = 9.8Hz), 5.77 (1H, d, J = 5.8Hz),
5.85-6.00 (1H, m), 7.46 (2H, t, J = 7.3Hz), 7.58 (1H, t, J = 7.3Hz),
8.07 (2H, d, J = 7.3Hz).
[0186]
Step 5: 9β-7-O-allyl-10-deacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
The title compound was obtained as a colorless and transparent syrupy substance by carrying out the same reaction operation as in Step 4 of Example 1 using the compound obtained in Step 4 above.
[0187]
Rf = 0.05 (Hexane: Ethyl acetate = 2: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.12 (3H, s), 1.40 (3H, s), 1.54 (3H, s), 1.55 (3H, s), 1.58 (3H, s),
1.74 (1H, s), 1.94 (3H, s), 1.99-2.38 (4H, m), 2.3 (3H, s),
3.22 (1H, d, J = 5.4Hz), 3.57 (1H, dd, J = 6.9Hz, 2.5Hz),
3.83 (1H, dd, J = 12.4Hz, 5.6Hz), 4.09-4.27 (2H, m), 4.23 (1H, d, J = 7.7Hz),
4.60 (1H, d, J = 7.7Hz), 4.72-4.88 (2H, m), 5.11 (1H, dd, J = 10.3Hz, 1.4Hz),
5.26 (1H, dd, J = 17.0Hz, 1.4Hz), 5.52 (1H, d, J = 7.3Hz), 5.81-5.96 (2H, m),
7.46 (2H, t, J = 7.8Hz), 7.58 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz).
[0188]
Step 6: 9β-7-O-allyl-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10 -Deacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
Using the compound obtained in the above step 5, 1- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyloxy) -4-phenylazetidine-2- Reaction with ON gave the title compound as a clear, colorless syrup.
[0189]
Rf = 0.17 (hexane: ethyl acetate = 2: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.32 (3H, s), -0.12 (3H, s), 0.74 (9H, s), 1.25 (3H, s), 1.36 (3H, s),
1.36 (9H, s), 1.51 (3H, s), 1.53 (3H, s), 1.57 (3H, s), 1.75 (3H, s),
2.06-2.12 (2H, m), 2.15-2.35 (1H, m), 2.42 (1H, dd, J = 14.7Hz, 9.8Hz),
2.53 (3H, s), 3.22 (1H, d, J = 5.9Hz), 3.46 (1H, dd, J = 9.8Hz, 2.0Hz),
3.85 (1H, dd, J = 12.2Hz, 5.4Hz), 4.18 (1H, dd, J = 12.2Hz, 5.8Hz),
4.28 (1H, AB type d, J = 8.3Hz), 4.58 (1H, AB type d, J = 8.3Hz),
4.33 (1H, d, J = 8.8Hz), 4.50 (1H, s), 4.83 (1H, t, J = 6.8Hz),
5.15 (1H, dd, J = 10.7Hz, 1.4Hz), 5.22-5.36 (1H, m),
5.31 (1H, dd, J = 17.2Hz, 1.4Hz), 5.40 (1H, d, J = 8.8Hz), 5.41-5.54 (1H, m),
5.87 (1H, d, J = 5.9Hz), 5.81-5.98 (1H, m), 6.22 (1H, t, J = 8.8Hz),
7.19-7.42 (5H, m), 7.47 (2H, t, J = 7.3Hz), 7.57 (1H, t, J = 7.3Hz),
8.11 (2H, d, J = 7.3Hz).
[0190]
Step 7: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-9-dihydro -7-O- (2,3-Dihydroxypropyl) -9,10-O-isopropylidenebaccatin III
Using the compound obtained in the above Step 6, the title compound was obtained as a colorless transparent syrup-like substance by the same reaction operation as in Step 1 of Example 8.
[0191]
Rf = 0.29 (chloroform: acetone = 4: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.32 (3H, s), -0.11 (3H, s), 0.74 (9H, s), 1.31 (3H, s), 1.37 (9H, s),
1.39 (3H, s), 1.52 (3H, s), 1.57 (3H, s), 1.60 (3H, s), 1.74 (3H, s),
1.94-2.42 (m), 2.53 (3H, s), 3.03 and 3.06 (total 1H, each d, J = 4.9Hz),
3.45-3.81 (m), 3.88-4.02 (m), 4.21-4.38 (m), 4.47 (d, J = 7.7Hz),
4.50-4.58 (m), 4.90-5.01 (m), 5.23-5.36 (m), 5.40-5.54 (m),
5.92 and 5.94 (total 1H, each d, J = 4.9Hz), 5.94 (d, J = 4.9Hz),
7.21-7.40 (5H, m), 7.48 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz),
8.13 (2H, d, J = 7.8Hz).
[0192]
Step 8: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-9-dihydro -7-O- (2-morpholinoethyl) -9,10-O-isopropylidenebaccatin III The title compound was purified by the same reaction procedure as in Step 2 of Example 8 using the compound obtained in Step 7 above. Obtained as a clear syrupy material.
[0193]
Rf = 0.74 (chloroform: methanol = 12: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.33 (3H, s), -0.12 (3H, s), 0.74 (9H, s), 1.26 (3H, s), 1.35 (9H, s),
1.39 (3H, s), 1.50 (3H, s), 1.52 (3H, s), 1.57 (3H, s), 1.74 (3H, s),
1.59-1.80 (4H, m), 2.05-2.33 (3H, m), 2.36-2.52 (3H, m), 2.52 (3H, s),
3.18 (1H, d, J = 5.4Hz), 3.35-3.49 (2H, m), 3.60-3.84 (5H, m),
4.19-4.33 (1H, m), 4.26 (1H, AB type d, J = 8.3Hz),
4.55 (1H, AB type d, J = 8.3Hz), 4.50 (1H, s), 4.83 (1H, t, J = 6.4Hz),
5.30 (1H, broad d, J = 8.0Hz), 5.86 (1H, d, J = 5.4Hz), 6.22 (1H, t, J = 8.8Hz),
7.28-7.41 (5H, m), 7.48 (2H, t, J = 7.8Hz), 7.58 (1H, t, J = 7.8Hz),
8.11 (2H, d, J = 7.8Hz).
[0194]
Step 9: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-7-O- (2 -Morpholinoethyl) -9,10-O-isopropylidenebaccatin III
The title compound was obtained as a colorless and transparent syrupy substance by the same reaction procedure as in Step 4 of Example 1 using the compound obtained in Step 8 above.
[0195]
Rf = 0.23 (chloroform: methanol = 15: 1 (v / v))
Melting point: 128-133 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23 (3H, s), 1.39 (9H, s), 1.41 (3H, s), 1.51 (3H, s), 1.58 (6H, s),
1.59 (3H, s), 1.50-1.86 (2H, m), 1.81 (1H, broad s), 1.96-2.47 (4H, m),
2.30 (3H, s), 2.48-2.62 (4H, m), 3.03 (1H, d, J = 4.0Hz), 3.32-3.43 (1H, m),
3.46-3.57 (1H, m), 3.59-3.84 (4H, m), 4.07-4.23 (2H, m),
4.52 (1H, d, J = 7.8Hz), 4.60 (1H, s), 4.83 (1H, s),
5.22-5.33 (1H, broad d, J = 8.4Hz), 5.46 (1H, d, J = 7.8Hz),
5.59 (1H, broad d, J = 8.4Hz), 5.93 (1H, d, J = 4.0Hz), 6.10 (1H, t, J = 8.3Hz),
7.21-7.43 (5H, m), 7.47 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz),
8.11 (2H, d, J = 7.8Hz).
[0196]
Example 11
[0197]
Embedded image
Step 1: 9β-13-O-[(2R, 3S) -N- (tert-butoxycarbonyl) -N, O- (4-methoxybenzylidene) -3-phenylisoserinyl] -10-deacetyl-9- Dihydro-9,10-O- (2-propenylidene) -7-O- (2,2,2-trichloroethoxycarbonyl) baccatin III
70.1 mg of (2R, 3S) -N- (tert-butoxycarbonyl) -N, O- (4-methoxybenzylidene) -3-phenylisoserine was mixed with 2.1 ml of dry methylene chloride and 2.1 ml of dry toluene. After dissolution, 34.0 mg of dicyclohexylcarbodiimide was added at 0 ° C. After 12 minutes, a solution prepared by dissolving 78.1 mg of the compound obtained in Step 1 of Example 9 in 2.5 ml of dry methylene chloride was added dropwise, 4.2 mg of 4-dimethylaminopyridine was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was cooled to 0 ° C., and the filtrate was washed with toluene. The filtrate was diluted with chloroform, washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: acetone = 20: 1 (v / v)) to obtain 68.9 mg of the title compound as a white glassy substance. It was.
[0199]
Rf = 0.18 (chloroform: acetone = 20: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.05 (12H, s), 1.24 (3H, s), 1.45 (3H, br-s), 1.58 (3H, s), 1.74 (3H, br-s),
1.77 (1H, s), 2.07 (1H, d, J = 14.7Hz, J = 8.3Hz), 2.13-2.35 (3H, m),
3.04 (1H, d, J = 4.9Hz), 3.81 (3H, s), 3.93 (1H, d, J = 7.8Hz),
4.24 (1H, d, J = 8.3Hz), 4.35 (1H, d, J = 8.3Hz), 4.58 (1H, d, J = 4.9Hz),
4.65 (1H, d, J = 11.7HZ), 4.79 (1H, t, J = 4.9Hz), 4.83 (1H, d, J = 11.7Hz),
5.03 (1H, dd, J = 6.9Hz, J = 4.0Hz), 5.10 (1H, d, J = 5.9Hz), 5.20 (1H, d, J = 7.8Hz),
5.34-5.48 (1H, br), 5.45 (1H, d, J = 10.2Hz), 5.55 (1H, d, J = 17.1Hz),
5.87 (1H, d, J = 4.9Hz), 5.93-6.1 (2H, m), 6.25-6.46 (1H, br),
6.90 (2H, d, J = 8.8Hz), 7.32-7.52 (7H, m), 7.47 (2H, t, J = 7.3Hz),
7.60 (1H, t, J = 7.3Hz), 8.05 (2H, d, J = 7.3Hz).
[0200]
Step 2: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- Propylidene-7-O- (2,2,2-trichloroethoxycarbonyl) baccatin III
Dissolve 68.9 mg of the compound obtained in the above step 1 in 3.4 ml of ethanol, add 8.6 mg of 10% palladium hydroxide at room temperature, stir for 5 hours under hydrogen atmosphere, and again add 8.6 mg of 10% palladium hydroxide. And stirred for 2 hours. The reaction system was replaced with nitrogen, and the reaction solution was filtered. The filtrate was washed with ethyl acetate, the solvent of the filtrate was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: acetone = 20: 1 (v / v)), The title compound (28.4 mg) was obtained as a white glassy substance.
[0201]
Rf = 0.40 (chloroform: acetone = 20: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.03 (3H, t, J = 7.8Hz), 1.25 (3H, s), 1.40 (9H, s), 1.59 (3H, s), 1.61 (3H, s),
1.64 (3H, s), 1.74-1.93 (3H, m), 2.01-2.23 (2H, m), 2.30 (3H, s),
2.30-2.45 (2H, m), 3.04 (1H, d, J = 4.9Hz), 3.88 (1H, d, J = 7.3Hz),
4.21-4.34 (2H, m), 4.43 (1H, d, J = 8.3Hz), 4.62 (1H, br-s),
4.65 (1H, d, J = 12.2Hz), 4.76 (1H, t, J = 5.4Hz), 4.85 (1H, d, J = 12.2Hz),
4.90 (1H, br-s), 5.14 (1H, br-t, J = 4.4Hz), 5.24 (1H, d, J = 7.3Hz),
5.31 (1H, d, J = 9.2Hz), 5.66 (1H, d, J = 9.2Hz), 6.00 (1H, d, J = 4.9Hz),
6.09 (1H, t, J = 7.8Hz), 7.20-7.46 (5H, m), 7.47 (2H, t, J = 7.3Hz),
7.60 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
[0202]
Step 3: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- Propyridenebaccatin III
28.4 mg of the compound obtained in Step 2 above was dissolved in 2.8 ml of a mixed solvent of dioxane-methanol-acetic acid (1: 1: 1 (v / v)), 66.2 mg of zinc powder was added at room temperature, and the mixture was stirred for 5 hours. Then, it stirred at 55 degreeC for 16 hours. The reaction solution was filtered as it was, the filtrate was washed with chloroform, and the solvent of the filtrate was distilled off under reduced pressure. The obtained residue was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: acetone = 10: 1 (v / v)) to obtain 10.8 mg of the title compound as a white glassy substance. .
[0203]
Rf = 0.18 (chloroform: acetone = 20: 1 (v / v))
Melting point 132-139 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.04 (3H, t, J = 7.9Hz), 1.26 (6H, s), 1.40 (9H, s), 1.60 (3H, s), 1.66 (3H, s),
1.73-1.91 (2H, m), 1.88 (1H, s), 1.98-2.14 (2H, m), 2.17-2.33 (1H, m),
2.30 (3H, s), 2.37 (1H, dd, J = 15.1Hz, J = 9.7Hz), 2.91 (1H, d, J = 4.8Hz),
3.78 (1H, d, J = 7.3Hz), 4.02-4.19 (2H, m), 4.33 (1H, d, J = 8.3Hz),
4.37 (1H, d, J = 8.3Hz), 4.55-4.68 (2H, m), 4.80 (1H, t, J = 5.4Hz),
5.10 (1H, s like), 5.19 (1H, d, J = 7.3Hz), 5.29 (1H, br-d, J = 8.3Hz),
5.63 (1H, br-d, J = 8.3Hz), 6.05 (1H, d, J = 4.8Hz), 6.08 (1H, t, J = 8.8Hz),
7.20-7.45 (5H, m), 7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.10 (2H, d, J = 7.8Hz).
FAB Mass: 850 (M++1).
[0204]
Example 12
[0205]
Embedded image
Step 1: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O- (4-nitrophenoxycarbonyl) baccatin III
70 mg of the compound obtained in Step 2 of Example 1 was dissolved in 2 ml of dried tetrahydrofuran and cooled to -78 ° C. Next, 0.16 ml of normal butyl lithium (1.64 mol / ml hexane solution) was added dropwise at the same temperature. After completion of dropping, the mixture was stirred at the same temperature for 10 minutes. Then, a solution of 29 mg of 4-nitrophenyl chloroformate dissolved in 1 ml of tetrahydrofuran was added dropwise at the same temperature. After stirring for 1 hour, the reaction solution was gradually warmed to 0 ° C. and stirred for 2 hours. A saturated ammonium chloride solution was added to the reaction mixture, and the mixture was diluted with ethyl acetate and extracted. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: acetone = 97: 3 (v / v)) to obtain 23 mg of the title compound.
[0207]
1H-NMR (CDClThree/ TMS) δ (ppm):
1.18 (3H, s), 1.43 (3H, s), 1.57 (3H, s), 1.59 (3H, s), 1.62 (3H, s),
1.63-1.80 (1H, m), 1.90-2.09 (2H, m), 1.96 (3H, s), 2.25-2.41 (1H, m),
2.36 (3H, s), 3.18 (1H, d, J = 5Hz), 3.94 (1H, d, J = 7Hz), 4.18 (1H, J = 8Hz),
4.25 (1H, 8Hz), 4.78-4.89 (1H, m), 4.83-4.88 (1H, m), 5.13-5.17 (1H, m),
5.63 (1H, d, J = 7Hz), 5.94 (1H, d, J = 5Hz), 7.31 (2H, d, J = 9Hz),
7.49 (2H, t, J = 8Hz), 7.55-7.60 (1H, m), 8.12 (2H, d, J = 7Hz),
8.21 (2H, d, J = 9Hz).
[0208]
Step 2: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O-[(4-methylpiperazin-1-yl) carbonyl] baccatin III
50 mg of N-methylpiperazine was added dropwise at room temperature to a solution obtained by dissolving 37 mg of the compound obtained in the above step 1 in 2 ml of acetonitrile. After stirring at the same temperature for 5 hours, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: methanol = 95: 5 (v / v)) to obtain 9 mg of the title compound.
[0209]
1H-NMR (CDClThree/ TMS) δ (ppm):
1.14 (3H, s), 1.38 (3H, s), 1.52 (3H, s), 1.55 (3H, s), 1.56 (3H, s),
1.68-1.80 (1H, m), 1.95 (3H, s), 2.01-2.16 (2H, m), 2.27 (3H, s),
2.24-2.38 (5H, m), 2.34 (3H, s), 3.24 (1H, d, J = 5Hz), 3.30-3.57 (4H, m),
4.04 (1H, d, J = 8Hz), 4.29 (1H, J = 8Hz), 4.43 (1H, 8Hz), 4.79-4.87 (1H, m),
4.84 (1H, d, J = 4Hz), 5.16-5.19 (1H, m), 5.56 (1H, d, J = 8Hz),
5.92 (1H, d, J = 5Hz), 7.49 (2H, t, J = 8Hz), 7.61 (1H, t, J = 8Hz),
8.15 (2H, d, J = 7Hz).
[0210]
Step 3: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-9-dihydro -9,10-O-isopropylidene-7-O-[(4-methylpiperazin-1-yl) carbonyl] baccatin III
1- (tert-Butoxycarbonyl) -3- (tert-butyldimethylsilyloxy) -4-phenylazetidin-2-one was prepared in the same manner as in Step 3 of Example 1 using the compound obtained in Step 2 above as a raw material. To give the title compound as a white amorphous solid.
[0211]
1H-NMR (CDClThree/ TMS) δ (ppm):
-0.33 (3H, s), -0.12 (3H, s), 0.74 (9H, s), 1.25 (3H, s), 1.28 (3H, s),
1.33 (6H, s), 1.36 (3H, s), 1.53 (3H, s), 1.55 (9H, s), 1.63-1.80 (1H, m),
1.75 (3H, s), 2.00-2.20 (2H, m), 2.31 (3H, s), 2.20-2.45 (5H, m),
2.54 (3H, s), 3.21 (1H, d, J = 5Hz), 3.39-3.64 (4H, m), 4.12 (1H, d, J = 9Hz),
4.32 (1H, d, J = 8Hz), 4.47 (1H, d, J = 8Hz), 4.52 (1H, brs), 4.91 (1H, m),
5.10 (1H, m), 5.28-5.33 (1H, m), 5.44 (1H, d, J = 9Hz), 5.42-5.49 (1H, m),
5.89 (1H, d, J = 5Hz), 6.20-6.23 (1H, m), 7.23-7.40 (5H, m),
7.50 (2H, t, J = 8Hz), 7.60 (1H, t, J = 8Hz), 8.14 (2H, d, J = 8Hz).
[0212]
Step 4: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- Isopropylidene-7-O-[(4-methylpiperazin-1-yl) carbonyl] baccatin III 13 mg of the compound obtained in step 3 above is dissolved in 1 ml of distilled pyridine and 0.2 ml of hydrogen fluoride at 0 ° C. -Pyridine was added. After completion of the dropwise addition, the mixture was warmed to room temperature and stirred overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: methanol = 95: 5 (v / v)) to obtain 5 mg of the title compound.
[0213]
1H-NMR (CDClThree/ TMS) δ (ppm):
1.24 (3H, s), 1.37 (3H, s), 1.39 (3H, s), 1.53 (3H, s), 1.56 (9H, s),
1.60-1.80 (1H, m), 1.62 (3H, s), 2.00-2.20 (2H, m), 2.20-2.42 (5H, m),
2.26 (3H, s), 2.32 (3H, s), 3.09 (1H, d, J = 5Hz), 3.31-3.58 (4H, m),
4.03 (1H, d, J = 9Hz), 4.27 (1H, d, J = 8Hz), 4.41 (1H, d, J = 8Hz),
4.62 (1H, broad s), 4.88 (1H, m), 5.16 (1H, m), 5.30 (1H, m),
5.49 (1H, d, J = 7Hz), 5.59 (1H, m), 5.95 (1H, m), 6.10 (1H, brt, J = 8Hz),
7.23-7.40 (5H, m), 7.49 (2H, t, J = 8Hz), 7.61 (1H, t, J = 7Hz),
8.13 (2H, d, J = 7Hz).
[0214]
Example 13
[0215]
Embedded image
Step 1: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-9-dihydro -9,10-O-isopropylidene-7-O- (2-dimethylaminoethyl) baccatin III
Using the compound obtained in Step 7 of Example 10 as a raw material and using dimethylamine instead of morpholine, the same operation as in Step 2 of Example 8 was performed to obtain the title compound as a white glassy solid. It was.
[0217]
Rf = 0.53 (chloroform: methanol = 5: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.32 (3H, s), -0.11 (3H, s), 0.75 (9H, s), 1.27 (3H, s), 1.36 (9H, s),
1.40 (3H, s), 1.52 (3H, s), 1.55 (3H, s), 1.57 (3H, s), 1.74 (3H, s),
2.09-2.26 (2H, m), 2.31-2.51 (8H, m), 2.53 (3H, s), 2.63-2.86 (2H, m),
3.13 (1H, d, J = 5.3Hz), 3.46-3.63 (2H, m), 3.76-3.89 (1H, br),
4.12-4.25 (1H, br), 4.28 (1H, d, J = 7.8Hz), 4.49 (1H, d, J = 7.8Hz),
4.52 (1H, br), 4.90 (1H, t, J = 4.4Hz), 5.22-5.36 (1H, m), 5.38-5.52 (2H, m),
5.88 (1H, d, J = 5.3Hz), 6.21 (1H, t, J = 8.5Hz), 7.19-7.41 (5H, m),
7.50 (2H, t, J = 7.4Hz), 7.59 (1H, t, J = 7.4Hz), 8.11 (2H, d, J = 7.4Hz).
[0218]
Step 2: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- Isopropylidene-7-O- (2-dimethylaminoethyl) baccatin III
The title compound was obtained as a white glassy solid by carrying out the same operation as in Step 5 of Example 3 using the compound obtained in Step 1 as a raw material.
[0219]
Rf = 0.32 (chloroform: acetone = 20: 1 (v / v))
Melting point 119-121 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.22 (3H, s), 1.38 (9H, s), 1.41 (3H, s), 1.51 (3H, s), 1.58 (9H, s),
1.80 (1H, s), 2.04-2.37 (10H, m), 2.26 (3H, s), 2.52 (2H, t like, J = 5.9Hz),
3.04 (1H, d, J = 4.4Hz), 3.31-3.43 (1H, m), 3.46-3.57 (1H, m),
3.70-3.81 (1H, m), 4.14-4.28 (1H, br), 4.20 (1H, d, J = 7.8Hz),
4.51 (1H, d, J = 7.8Hz), 4.60 (1H, s like), 4.84 (1H, t like, J = 5.0Hz),
5.27 (1H, br-d, J = 8.0Hz), 5.46 (1H, d, J = 7.6Hz), 5.59 (1H, br-d, J = 8.0Hz),
5.92 (1H, d, J = 4.4Hz), 6.10 (1H, t, J = 7.8Hz), 7.21-7.43 (5H, m),
7.47 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).
FAB Mass: 921 (M+).
[0220]
Example 14
[0221]
Embedded image
Step 1: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyloxy) -3-phenylpropionyl] -10-deacetyl-9-dihydro -7-O-Carboxymethyl-9,10-O-isopropylidenebaccatin III
67.2 mg of the compound obtained in Step 7 of Example 10 was dissolved in 3 ml of a mixed solvent of tetrahydrofuran-methanol-water (1: 1: 1 (v / v)), and 55.3 mg of sodium metaperiodate was added at room temperature. And stirred for 1 hour. Water cooled at 0 ° C. was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. Evaporate the solvent under reduced pressure, dissolve 22.0 mg of the remaining 48.0 mg in 1.65 ml of dioxane and 0.55 ml of water, add 5.6 mg of sulfamic acid and 5.3 mg of sodium chlorite at room temperature, and stir for 30 minutes. did. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: methanol = 15: 1 (v / v)) to obtain 21.3 mg of the title compound as a white solid substance. .
[0223]
Rf = 0.39 (chloroform: methanol = 10: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.32 (3H, s), -0.11 (3H, s), 0.74 (9H, s), 1.33 (3H, s), 1.37 (9H, s),
1.39 (3H, s), 1.58 (6H, s), 1.63 (3H, s), 1.74 (3H, s), 1.81 (1H, s),
2.02-2.40 (4H, m), 2.54 (3H, s), 3.04 (1H, d, J = 4.9Hz), 3.68 (1H, br),
3.80-4.03 (2H, m), 4.33 (1H, d, J = 7.8Hz), 4.54 (1H, d, J = 7.8Hz),
4.44-4.62 (1H, m), 5.05 (1H, br), 5.30 (1H, d, J = 8.3Hz),
5.45 (1H, d, J = 8.3Hz), 5.52 (1H, d, J = 7.3Hz), 5.94 (1H, d, J = 4.9Hz),
6.20 (1H, t, J = 8.8Hz), 7.18-7.42 (5H, m), 7.49 (2H, t, J = 7.9Hz),
7.60 (1H, t, J = 7.9Hz), 8.12 (2H, d, J = 7.9Hz).
[0224]
Step 2: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-7-O-carboxymethyl -9,10-O-isopropylidenebaccatin III
The title compound was obtained as a white glassy solid by performing the same operation as in Step 5 of Example 3 using the compound obtained in Step 1 above as a raw material.
[0225]
Rf = 0.40 (chloroform: methanol = 10: 1 (v / v))
Melting point 157-160 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.40 (3H, s), 1.41 (9H, s), 1.53 (3H, s), 1.56 (3H, s),
1.58 (3H, s), 1.63 (3H, s), 1.86 (1H, s), 1.92-2.13 (2H, m),
2.26-2.44 (2H, m), 2.32 (3H, s), 2.95 (1H, d, J = 4.4Hz), 3.71 (1H, br-s),
3.78 (1H, br-d, J = 6.0Hz), 3.90 (1H, d, J = 6.6Hz), 3.97-4.11 (1H, br),
4.29 (1H, d, J = 8.3Hz), 4.30-4.44 (1H, m), 4.54 (1H, d, J = 8.3Hz),
4.62 (1H, br-s), 5.04 (1H, br-s), 5.27 (1H, d, J = 8.3Hz),
5.53 (1H, d, J = 6.8Hz), 5.60 (1H, d, J = 8.3Hz), 5.97 (1H, d, J = 4.4Hz),
6.10 (1H, t, J = 7.8Hz), 7.22-7.43 (5H, m), 7.47 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
FAB Mass: 908 (M++1).
[0226]
Example 15
[0227]
Embedded image
Step 1: 9β-13-O- [3- (tert-butoxycarbonylamino) -2-methyl-2-triethylsilyloxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O— Isopropylidene-7-O-triethylsilylbaccatin III
Using the compound obtained in Step 3 of Example 3 as a starting material, cis-1- (tert-butoxycarbonyl) -3-methyl-4-phenyl-3- (triethylsilyloxy) was prepared in the same manner as in Step 3 of Example 1. Reaction with azetidin-2-one gave the title compound as a colorless glassy solid.
[0229]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.50-0.72 (12H, m), 0.87 (9H, t, J = 8Hz), 0.97 (9H, t, J = 8Hz), 1.29 (9H, s),
1.34 (3H, s), 1.38 (3H, s), 1.41 (3H, s), 1.51 (3H, s), 1.57 (3H, s),
1.59 (3H, s), 1.73 (3H, s), 2.00-2.18 (3H, m), 2.34 (1H, dd, J = 15Hz, 10Hz),
2.64 (3H, s), 3.07 (1H, d, J = 5.5Hz), 4.00 (1H, dd, J = 8Hz, 3.5Hz),
4.24 (1H, d, J = 8Hz), 4.34 (1H, br-d, J = 8Hz), 4.56 (1H, d, J = 8Hz),
4.86 (1H, t, J = 5.5Hz), 4.98 (1H, d, J = 10Hz), 5.42 (1H, d, J = 9Hz),
5.52 (1H, d, J = 10Hz), 5.91 (1H, d, J = 5.5Hz), 6.28 (1H, t, J = 9Hz),
7.27-7.36 (10H, m), 7.48 (2H, t, J = 7.5Hz), 7.58 (1H, t, J = 7.5Hz),
8.15 (2H, d, J = 7.5Hz).
[0230]
Step 2: 9β-13-O- [3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O-isopropylidene Baccatin III
The compound obtained in the above Step 1 was reacted in the same manner as in Step 4 of Example 1 to obtain the title compound as a colorless glassy solid.
[0231]
Melting point 180-182 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.32 (3H, s), 1.35 (9H, s), 1.40 (6H, s), 1.58 (3H, s), 1.60 (3H, s),
1.64 (3H, s), 1.68 (3H, s), 2.08-2.31 (4H, m), 2.51 (3H, s),
2.91 (1H, d, J = 4.5Hz), 3.80 (1H, d, J = 7Hz), 3.99 (1H, s), 4.08 (1H, m),
4.36 (1H, AB type d, J = 9Hz), 4.39 (1H, AB typed, J = 9Hz), 4.70 (1H, d, J = 8Hz),
5.01 (1H, d, J = 10Hz), 5.11 (1H, br-s), 5.50 (1H, d, J = 7Hz),
5.67 (1H, d, J = 10Hz), 6.05 (1H, d, J = 4.5Hz), 6.22 (1H, t, J = 8Hz),
7.28-7.41 (10H, m), 7.48 (2H, t, J = 7.5Hz), 7.60 (1H, t, J = 7.5Hz),
8.13 (1H, d, J = 7.5).
FAB Mass: 865 (M++1).
[0232]
Example 16
[0233]
Embedded image
Step 1: 9β-13-O-[(2R, 3S) -N- (tert-butoxycarbonyl) -N, O- (4-methoxybenzylidene) -3-phenylisoserinyl] -10-deacetyl-9- Dihydro-9,10-O- (propenylidene) baccatin III
Using the compound obtained in Step 1 of Example 11 as a raw material, the title compound was obtained as a glassy solid by conducting the same reaction operation as in Step 3 of Example 11.
[0235]
Rf = 0.35 (chloroform: acetone = 15: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.04 (12H, s), 1.27 (3H, s), 1.43 (3H, br s), 1.64 (3H, s), 1.72 (3H, br s),
1.83 (1H, s), 1.97-2.27 (4H, m), 2.82 (1H, d, J = 5.3Hz), 3.81 (3H, s),
3.85 (1H, d, J = 7.4Hz), 3.96-4.07 (1H, m), 4.22 (1H, d, J = 8.3Hz),
4.32 (1H, d, J = 8.3Hz), 4.48 (1H, d, J = 7.4Hz), 4.58 (1H, d, J = 5.4Hz),
4.98 (1H, s like), 5.17 (2H, d, J = 5.9Hz), 5.32-5.49 (1H, br),
5.44 (1H, d, J = 10.8Hz), 5.55 (1H, d, J = 17.8Hz), 5.90-6.12 (3H, m),
6.22-6.47 (1H, br), 6.90 (2H, d, J = 8.8Hz), 7.31-7.50 (9H, m),
7.59 (1H, t, J = 7.4Hz), 8.03 (2H, d, J = 7.4Hz).
[0236]
Step 2: 9β-13-O-[(2R, 3S) -N- (tert-butoxycarbonyl) -N, O- (4-methoxybenzylidene) -3-phenylisoserinyl] -10-deacetyl-9- Dihydro-9,10-O- (2-N-morpholinoethylidene) baccatin III
149.4 mg of the compound obtained in the above step 1 is dissolved in a mixed solvent of 4.48 ml of tetrahydrofuran and 1.49 ml of water, and 87.2 mg of N-methylmorpholine-N-oxide and 7.8 mg of osmium tetraoxide are added at room temperature. After stirring for hours, 3.6 mg of osmium tetraoxide was added and stirred for 16 hours. A saturated aqueous sodium sulfite solution was added, and the mixture was stirred at room temperature for 10 minutes and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was dissolved in 4.1 ml of a mixed solvent of tetrahydrofuran, water, and methanol (1: 1: 1 (v / v)), 118.6 mg of sodium metaperiodate was added at room temperature, and the mixture was stirred for 40 minutes. . The mixture was cooled to 0 ° C., cold water was added, saturated brine was further added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. Evaporate the solvent under reduced pressure, dissolve 65.2 mg of the resulting residue (126.2 mg) in ethanol (4 ml), add acetic acid (0.04 ml), morpholine (0.059 ml), and 10% palladium hydroxide (14.0 mg) at room temperature. For 5 hours. The reaction system was purged with nitrogen, the contents were filtered, the filtrate was distilled off under reduced pressure, and the resulting residue was subjected to silica gel thin layer chromatography (developing solvent; chloroform: acetone = 5: 1 (v / v)). To obtain 18.4 mg of the title compound as a colorless transparent syrup.
[0237]
Rf = 0.17 (chloroform: acetone = 5: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.04 (3H, s), 1.27 (3H, s), 1.41 (3H, br s), 1.56 (3H, s), 1.61 (3H, s),
1.71 (3H, br s), 1.99-2.25 (4H, m), 2.52-2.86 (7H, m), 3.66-3.86 (5H, m),
3.81 (3H, s), 4.00 (1H, br s), 4.21 (1H, d, J = 8.3Hz), 4.32 (1H, d, J = 8.3Hz),
4.57 (1H, d, J = 4.9Hz), 4.92-5.03 (2H, m), 5.10 (1H, d, J = 7.4Hz),
5.40 (1H, br), 5.93 (1H, d, J = 4.9Hz), 6.05 (1H, br), 6.20-6.48 (1H, br),
6.90 (2H, d, J = 8.8Hz), 7.31-7.51 (9H, m), 7.60 (1H, t, J = 7.3Hz),
8.03 (2H, d, J = 7.3Hz).
[0238]
Step 3: 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl-10-deacetyl-9-dihydro-9,10-O- ( 2-morpholinoethylidene) baccatin III
The title compound was obtained as a colorless and transparent syrupy substance by performing the same reaction operation as in Step 2 of Example 11 using the compound obtained in Step 2 above as a raw material.
[0239]
Rf = 0.20 (chloroform: acetone = 15: 1 (v / v))
Melting point: 129-132 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (6H, s), 1.40 (9H, s), 1.59 (3H, s), 1.65 (3H, s), 1.88 (1H, s),
1.96-2.46 (4H, m), 2.30 (3H, s), 2.50-2.70 (4H, m),
2.74 (1H, dd, J = 18.4Hz, J = 4.4Hz), 2.83 (1H, dd, J = 18.4Hz, J = 4.4Hz),
2.90 (1H, d, J = 4.9Hz), 3.63-3.86 (5H, m), 4.02-4.18 (2H, m),
4.32 (1H, d, J = 8.3Hz), 4.38 (1H, d, J = 8.3Hz), 4.63 (1H, s like),
4.66 (1H, d, J = 8.3Hz), 5.02 (1H, t, J = 3.9Hz), 5.10 (1H, s like),
5.19 (1H, d like, J = 6.9Hz), 5.29 (1H, d, J = 10.0Hz), 5.61 (1H, d, J = 10.0Hz),
6.00-6.13 (2H, m), 7.19-7.53 (7H, m), 7.59 (1H, t, J = 7.3Hz),
8.11 (2H, d, J = 7.3Hz).
FAB Mass: 921 (M+).
[0240]
The following compounds were synthesized in the same manner. In the table, Ph means a phenyl group.
[0241]
Embedded image
[Table 1]
[Table 2]
[Table 3]
[Table 4]
[Table 5]
Example 17
9 β-9,10-O- (2-benzylaminoethylidene) -13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10- Deacetyl-9-dihydrobaccatin III
[0248]
Melting point: 125-128 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.40 (9H, s), 1.56 (6H, s), 1.63 (3H, s), 1.80-2.45 (5H, m),
2.30 (3H, s), 2.89 (1H, d, J = 4.9Hz), 2.99 (2H, d, J = 4.9Hz),
3.80 (1H, d, J = 6.8Hz), 3.88 (2H, s), 4.08 (1H, br s), 4.31 (1H, d, J = 8.3Hz),
4.37 (1H, d, J = 8.3Hz), 4.62 (1H, s), 5.00 (1H, t, J = 4.9Hz), 5.10 (1H, s),
5.21 (1H, d, J = 6.8Hz), 5.29 (1H, d, J = 8.8Hz), 5.64 (1H, d, J = 8.8Hz),
6.00-6.15 (2H, m), 7.22-7.56 (7H, m), 7.60 (1H, t, J = 7.3Hz),
8.10 (2H, d, J = 7.3Hz).
FAB mass ： 941 (MH+)
[0249]
Example 18
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- [2 -(4-Thiomorpholinyl) ethylidene] baccatin III
[0250]
Melting point: 149-152 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.40 (9H, s), 1.56 (3H, s), 1.58 (3H, s), 1.64 (3H, s),
1.88 (1H, s), 2.00-2.45 (3H, m), 2.30 (3H, s), 2.62-2.96 (11H, m),
3.77 (1H, d, J = 7.3Hz), 4.03-4.21 (2H, m), 4.31 (1H, d, J = 8.8Hz),
4.38 (1H, d, J = 8.8Hz), 4.57-4.70 (2H, m), 4.99 (1H, t, J = 4.9Hz), 5.10 (1H, s),
5.18 (1H, d, J = 6.9Hz), 5.29 (1H, d, J = 8.3Hz), 5.62 (1H, d, J = 8.3Hz),
6.00-6.17 (2H, m), 7.23-7.46 (7H, m), 7.60 (1H, t, J = 7.4Hz),
8.10 (2H, d, J = 7.4Hz).
FAB mass ： 937 (MH+)
[0251]
Example 19
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- (2 -Dimethylaminoethylidene) Baccatin III
[0252]
Melting point: 148-149 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.38 (9H, s), 1.55 (3H, s), 1.58 (3H, s), 1.64 (3H, s),
1.87 (1H, s), 1.9-2.43 (4H, m), 2.28 (3H, s), 2.35 (6H, s),
2.67 (1H, dd, J = 13.2Hz, J = 7.8Hz), 2.75 (1H, dd, J = 13.2Hz, J = 3.4Hz),
2.88 (1H, d, J = 4.9Hz), 3.76 (1H, d, J = 7.3Hz), 4.07 (1H, br s),
4.30 (1H, d, J = 8.8Hz), 4.36 (1H, d, J = 8.8Hz), 4.60 (2H, br s),
4.98 (1H, dd, J = 5.4Hz, J = 3.4Hz), 5.08 (1H, s), 5.18 (1H, d, J = 7.3Hz),
5.27 (1H, d, J = 9.3Hz), 5.61 (1H, d, J = 9.3Hz), 6.00-6.18 (2H, m),
7.20-7.55 (7H, m), 7.60 (1H, t, J = 7.8Hz), 8.09 (2H, d, J = 7.8Hz).
FAB mass ： 879 (MH+)
[0253]
Example 20
9 β-4-O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl- 9-Dihydro-9,10-O- (2-propenylidene) baccatin III
[0254]
Melting point: 125-128 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.02 (3H, t, J = 7.3Hz), 1.28 (3H, s), 1.41 (9H, s), 1.62 (3H, s), 1.69 (3H, s),
1.71 (3H, s), 1.75-1.94 (2H, m), 1.81 (1H, s), 2.10-2.28 (3H, m),
2.29-2.52 (3H, m), 2.54-2.68 (1H, m), 2.94 (1H, d, J = 4.9Hz),
3.79-3.95 (1H, br), 3.89 (1H, d, J = 6.8Hz), 4.04-4.16 (1H, m),
4.32 (1H, d, J = 8.7Hz), 4.39 (1H, d, J = 8.7Hz), 4.59 (1H, d, J = 8.3Hz),
4.70 (1H, s), 5.05 (1H, s), 5.21 (1H, d, J = 5.8Hz), 5.27 (1H, d, J = 6.8Hz),
5.27-5.40 (2H, m), 5.46 (1H, d, J = 10.2Hz), 5.57 (1H, d, J = 17.5Hz),
6.04 (1H, ddd, J = 17.5Hz, J = 10.2Hz, J = 5.8Hz), 6.08 (1H, d, J = 4.9Hz),
6.05-6.15 (1H, m), 6.33 (1H, d, J = 2.9Hz), 6.36 (1H, dd, J = 2.9Hz, J = 1.9Hz),
7.39 (1H, d, J = 1.9Hz), 7.47 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.8Hz),
8.12 (2H, d, J = 7.8Hz).
FAB mass ： 866 (MH+)
[0255]
Example 21
9 β-4-O-butanoyl-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4,10-dideacetyl-9-dihydro- 9,10-O- (2-propenylidene) baccatin III
[0256]
Melting point: 127-130 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.99 (3H, t, J = 7.3Hz), 1.26 (3H, s), 1.29 (3H, s), 1.40 (3H, s), 1.61 (3H, s),
1.67 (3H, s), 1.73-1.88 (2H, m), 1.92 (1H, br s), 2.00-2.46 (3H, m),
2.91 (1H, d, J = 4.9Hz), 3.86 (1H, d, J = 6.8Hz), 4.09 (1H, br s),
4.32 (1H, d, J = 8.8Hz), 4.38 (1H, d, J = 8.8Hz), 4.50-4.68 (2H, m),
5.04 (1H, s like), 5.21 (1H, d, J = 6.4Hz), 5.21-5.32 (2H, m),
5.45 (1H, d, J = 10.7Hz), 5.56 (1H, d, J = 17.1Hz), 5.62 (1H, d, J = 9.8Hz),
5.97-6.12 (3H, m), 7.22-7.52 (7H, m), 7.60 (1H, t, J = 7.8Hz),
8.11 (2H, d, J = 7.8Hz).
FAB mass ： 876 (MH+)
[0257]
Example 22
9 β-4-O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl- 9-Dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0258]
Melting point: 123-125 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.01 (3H, t, J = 7.3Hz), 1.27 (3H, s), 1.40 (9H, s), 1.61 (3H, s), 1.65 (3H, s),
1.69 (3H, s), 1.77-1.92 (2H, m), 1.88 (1H, s), 2.08-2.26 (2H, m),
2.31-2.60 (7H, m), 2.74 (1H, dd, J = 18.0Hz, J = 4.4Hz),
2.83 (1H, dd, J = 18.0Hz, J = 4.0Hz), 2.93 (1H, d, J = 4.9Hz),
3.73 (4H, t, J = 4.9Hz), 3.82 (1H, d, J = 6.9Hz), 4.05-4.12 (1H, m),
4.31 (1H, d, J = 8.3Hz), 4.39 (1H, d, J = 8.3Hz), 4.64-4.73 (2H, m),
5.02 (1H, t, J = 4.0Hz), 5.06 (1H, s like), 5.20 (1H, d, J = 6.9Hz), 5.33 (2H, s),
6.04 (1H, d, J = 4.9Hz), 6.08 (1H, br t, J = 8.0Hz), 6.33 (1H, d, J = 3.5Hz),
6.36 (1H, dd, J = 3.5Hz, J = 1.9Hz), 7.39 (1H, d, J = 1.9Hz), 7.48 (2H, t, J = 7.8Hz),
7.61 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz). FAB mass ： 939 (MH+)
[0259]
Example 23
9 β-4-O-butanoyl-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4,10-dideacetyl-9-dihydro- 9,10-O- (2-morpholinoethylidene) baccatin III
[0260]
Melting point: 130-132 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.99 (3H, t, J = 7.3Hz), 1.26 (3H, s), 1.40 (9H, s), 1.60 (3H, s), 1.64 (3H, s),
1.72-1.79 (2H, m), 1.80 (1H, s), 2.01-2.26 (3H, m), 2.30-2.43 (2H, m),
2.49-2.70 (5H, m), 2.75 (1H, dd, J = 13.2Hz, J = 4.9Hz),
2.83 (1H, dd, J = 13.2Hz, J = 3.9Hz), 2.89 (1H, d, J = 4.4Hz), 3.74 (4H, t, J = 4.4Hz),
3.78 (1H, d, J = 7.4Hz), 4.01-4.12 (2H, m), 4.32 (1H, d, J = 8.7Hz),
4.38 (1H, d, J = 8.7Hz), 4.62 (1H, br s), 4.66 (1H, d, J = 8.3Hz),
4.99-5.09 (2H, m), 5.19 (1H, d, J = 6.8Hz), 5.27 (1H, d, J = 9.3Hz),
5.60 (1H, d, J = 9.3Hz), 5.60 (1H, d, J = 9.3Hz), 5.98-6.10 (2H, m),
7.20-7.52 (7H, m), 7.61 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
FAB mass ： 949 (MH+)
[0261]
Example 24
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl-9-dihydro-4- O-propanoyl-9,10-O- (2-propenylidene) baccatin III
[0262]
Melting point: 135-137 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.29 (3H, s), 1.34 (3H, t, J = 7.8Hz), 1.40 (9H, s), 1.63 (3H, s), 1.69 (3H, s),
1.71 (3H, s), 1.90 (1H, s), 2.10-2.26 (3H, m), 2.31-2.44 (1H, m),
2.51-2.73 (2H, m), 2.94 (1H, d, J = 4.9Hz), 3.91 (1H, d, J = 7.4Hz),
4.09 (1H, br), 4.32 (1H, d, J = 8.8Hz), 4.40 (1H, d, J = 8.8Hz),
4.55 (1H, br d, J = 7.4Hz), 4.69 (1H, s), 5.03 (1H, s like),
5.21 (1H, d, J = 5.9Hz), 5.26 (1H, d, J = 7.4Hz), 5.29-5.39 (2H, m),
5.45 (1H, d, J = 10.7Hz), 5.57 (1H, d, J = 17.6Hz), 5.97-6.06 (3H, m),
6.33 (1H, d, J = 2.9Hz), 6.36 (1H, dd, J = 2.9Hz, J = 2.0Hz), 7.39 (1H, d, J = 2.0Hz),
7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz), 8.13 (2H, d, J = 7.8Hz).
FAB mass ： 852 (MH+)
[0263]
Example 25
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl-9-dihydro-9, 10-O- (2-morpholinoethylidene) -4-O-propionylbaccatin III
[0264]
Melting point: 145-148 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.28 (3H, s), 1.32 (3H, t, J = 7.6Hz), 1.40 (9H, s), 1.61 (3H, s), 1.66 (3H, s),
1.70 (3H, s), 1.89 (1H, s), 2.09-2.26 (3H, m), 2.51-2.70 (6H, m),
2.75 (1H, dd, J = 12.4Hz, J = 5.6Hz), 2.82 (1H, dd, J = 12.4Hz, J = 4.0Hz),
2.93 (1H, d, J = 4.9Hz), 3.74 (4H, t, J = 4.4Hz), 3.83 (1H, d, J = 7.4Hz),
4.04-4.12 (1H, m), 4.32 (1H, d, J = 8.3Hz), 4.41 (1H, d, J = 8.3Hz),
4.66 (1H, d, J = 8.3Hz), 4.66 (1H, s), 4.99-5.08 (2H, m), 5.20 (1H, d, J = 7.4Hz),
5.32 (2H, s like), 6.05 (1H, d, J = 4.9Hz), 6.10 (1H, br t, J = 7.8Hz),
6.33 (1H, d, J = 3.4Hz), 6.36 (1H, dd, J = 3.4Hz, J = 2.0Hz), 7.39 (1H, d, J = 2.0Hz),
7.48 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.8Hz), 8.13 (2H, d, J = 7.8Hz).
FAB mass ： 925 (MH+)
[0265]
Example 26
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4,10-dideacetyl-9-dihydro-9,10-O- (2-propenylidene) -4-O-propionylbaccatin III
[0266]
Melting point: 190-192 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.30 (3H, t, J = 7.8Hz), 1.40 (9H, s), 1.59 (6H, br s),
1.61 (3H, s), 1.68 (3H, s), 1.90 (1H, s), 2.02-2.24 (3H, m),
2.29-2.70 (4H, m), 2.91 (1H, d, J = 4.4Hz), 3.87 (1H, d, J = 6.9Hz),
3.99-4.16 (2H, m), 4.32 (1H, d, J = 8.3Hz), 4.40 (1H, d, J = 8.3Hz),
4.55 (1H, d, J = 8.3Hz), 4.61 (1H, br s), 5.03 (1H, s like), 5.19-5.32 (1H, m),
5.21 (1H, d, J = 6.4Hz), 5.25 (1H, d, J = 6.9Hz), 5.45 (1H, d, J = 10.7Hz),
5.50-5.62 (1H, m), 5.56 (1H, d, J = 17.1Hz), 5.99-6.13 (3H, m),
7.12-7.50 (7H, m), 7.60 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
FAB mass ： 862 (MH+)
[0267]
Example 27
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4,10-dideacetyl-9-dihydro-9,10-O- (2-morpholinoethylidene) -4-O-propionylbaccatin III
[0268]
Melting point: 137-139 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.27 (3H, s), 1.29 (3H, t, J = 7.3Hz), 1.39 (9H, s), 1.58 (3H, s),
1.65 (3H, s), 1.88 (1H, s), 2.02-2.26 (3H, m),
2.36 (1H, dd, J = 14.0Hz, J = 10.0Hz), 2.42-2.71 (4H, m),
2.75 (1H, dd, J = 14.0Hz, J = 4.8Hz), 2.83 (1H, dd, J = 14.0Hz, J = 3.8Hz),
2.90 (1H, d, J = 4.4Hz), 3.74 (1H, t, J = 4.4Hz), 3.79 (1H, d, J = 6.8Hz),
3.92-4.13 (2H, br), 4.32 (1H, d, J = 8.8Hz), 4.40 (1H, d, J = 8.8Hz),
4.56-4.67 (2H, m), 5.03 (1H, s like), 5.19 (1H, d, J = 6.8Hz),
5.22 (1H, br d, J = 9.2Hz), 5.55 (1H, d, J = 9.2Hz), 5.98-6.12 (2H, m),
7.11-7.50 (7H, m), 7.61 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
FAB mass ： 935 (MH+)
[0269]
Example 28
9 β-13-O-[(3S)-(tert-butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionyl] -10-deacetyl-9-dihydro-9,10-O- (2-propenylidene) baccatin III
[0270]
Melting point: 176-178 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (s), 1.44 (9H, s), 1.62 (s), 1.69 (s), 2.32 (s), 2.93 (1H, d, J = 5Hz),
3.89 (1H, d, J = 7Hz), 4.08 (1H, m), 4.28 (1H, d, J = 8.5Hz),
4.40 (1H, d, J = 8.5Hz), 4.61 (1H, d, J = 8.5Hz), 5.13 (1H, br),
5.20 (1H, d, J = 6Hz), 5.23 (1H, d, J = 7Hz), 5.38 (1H, d, J = 12Hz),
5.45 (1H, d, J = 11Hz), 5.56 (1H, d, J = 17Hz), 5.67 (1H, m), 6.03 (2H, m),
6.21 (1H, t, J = 9Hz), 6.39 (1H, dd, J = 3Hz, 2Hz), 6.44 (1H, d, J = 3Hz),
7.43 (1H, d, J = 2Hz), 7.48 (2H, t, J = 7.5Hz), 7.61 (1H, t, J = 7.5Hz),
8.11 (2H, d, J = 7.5Hz).
FAB mass ： 858 (M+)
[0271]
Example 29
9 β-13-O-[(3S)-(tert-butoxycarbonylamino) -2,2-difluoro-3- (2-furyl) propionyl] -10-deacetyl-9-dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0272]
Melting point: 142-144 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (s), 1.44 (9H, s), 1.61 (s), 1.66 (s), 2.19 (2H, m), 2.28 (2H, m),
2.32 (3H, s), 2.62 (4H, m), 2.74 (1H, dd, J = 13.5Hz, 5Hz),
2.81 (1H, dd, J = 13.5Hz, 5Hz), 2.91 (1H, d, J = 5Hz), 3.73 (4H, t, J = 4.5Hz),
3.81 (1H, d, J = 7.5Hz), 4.07 (1H, br), 4.28 (1H, d, J = 8.5Hz),
4.41 (1H, d, J = 8.5Hz), 4.72 (1H, d, J = 8.5Hz), 5.01 (1H, t, J = 4.5Hz),
5.14 (1H, br), 5.16 (1H, d, J = 7.5Hz), 5.38 (1H, d, J = 9Hz), 5.67 (1H, m),
6.01 (1H, d, J = 5Hz), 6.20 (1H, t, J = 9Hz), 6.39 (1H, dd, J = 3Hz, 2Hz),
6.43 (1H, d, J = 3Hz), 7.43 (1H, d, J = 2Hz), 7.49 (2H, t, J = 7.5Hz),
7.61 (1H, t, J = 7.5Hz), 8.11 (2H, d, J = 7.5Hz).
FAB mass ： 931 (M+)
[0273]
Example 30
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-7-O-methyl-9, 10-O- (2-propenylidene) baccatin III
[0274]
Melting point: 137-140 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.20 (3H, s), 1.40 (9H, br s), 1.57 (3H, s), 1.59 (3H, s), 1.65 (3H, s),
1.86 (1H, s), 1.95-2.50 (4H, m), 2.27 (3H, s), 3.07 (1H, d, J = 4.9Hz),
3.33-3.42 (1H, s), 3.38 (3H, s), 4.29 (1H, d, J = 8.1Hz), 4.32-4.40 (1H, br),
4.36 (1H, d, J = 8.1Hz), 4.46 (1H, d, J = 7.8Hz), 4.62 (1H, br s),
4.89 (1H, br d, J = 5.4Hz), 5.17 (1H, d, J = 5.9Hz), 5.25-5.38 (1H, m),
5.34 (1H, d, J = 8.3Hz), 5.48 (1H, d, J = 10.3Hz), 5.59 (1H, d, J = 17.6Hz),
5.66 (1H, br d, J = 9.3Hz), 5.96 (1H, d, J = 4.9Hz), 6.08 (1H, br t, J = 7.8Hz),
6.17 (1H, ddd, J = 5.9,10.3,17.6Hz), 7.26-7.44 (5H, m), 7.46 (2H, t, J = 7.3Hz),
7.59 (1H, t, J = 7.3Hz), 8.09 (2H, d, J = 7.3Hz)
FAB mass: 862 (MH+)
[0275]
Example 31
9 β-13-O-[(2R, 3S)-(3-tert-butoxycarbonylamino) -2-hydroxy-5-methyl-4-hexenoyl] -10-deacetyl-9-dihydro-9,10-O -(2-propenylidene) baccatin III
[0276]
Melting point: 122-127 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm):
1.25 (3H, s), 1.40 (9H, s), 1.62 (3H, s), 1.69 (3H, s), 1.75 (6H, s),
1.77 (3H, s), 2.04-2.38 (4H, m), 2.11 (3H, s), 2.63 (1H, s),
2.96 (1H, d, J = 7.5Hz), 4.11 (1H, m), 4.29 (1H, br),
4.36 (2H, AB type q, J = 8.5Hz), 4.58 (1H, d, J = 8.2Hz),
4.83 (1H, dt, J = 9.1Hz, J = 2.3Hz), 4.96 (1H, br), 5.12 (1H, s),
5.22 (1H, d, J = 6.1Hz), 5.27 (1H, d, J = 7.9Hz), 5.28 (1H, d, J = 6.1Hz),
5.45 (1H, d, J = 10.5Hz), 5.57 (1H, d, J = 17.1Hz), 5.94-6.12 (3H, m),
7.46 (2H, t, J = 7.8Hz), 7.50 (1H, t, J = 7.3Hz), 8.04 (2H, d, J = 6.8Hz).
FAB mass ： 826 (MH+).
[0277]
Example 32
9 β-9,10-O-[(2E) -4-Benzyloxy-2-butenylidene] -13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3 -Phenylpropionyl] -10-deacetyl-9-dihydrobaccatin III
[0278]
Melting point: 112-115 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.40 (9H, s), 1.59 (3H, br s), 1.62 (3H, s), 1.68 (3H, s),
1.90 (1H, s), 2.00-2.35 (3H, m), 2.29 (3H, s),
2.37 (1H, dd, J = 15.2Hz, J = 9.8Hz), 2.90 (1H, d, J = 4.4Hz),
3.85 (1H, d, J = 6.9Hz), 4.10 (2H, d, J = 4.4Hz), 4.14 (1H, br),
4.32 (1H, d, J = 8.3Hz), 4.37 (1H, d, J = 8.3Hz), 4.56 (2H, s), 4.62 (1H, br),
5.09 (1H, s like), 5.21-5.36 (3H, m), 5.64 (1H, br d, J = 9.8Hz),
5.95 (1H, dd, J = 15.6Hz, J = 5.8Hz), 6.04-6.16 (3H, m), 7.25-7.45 (10H, m),
7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
FAB mass ： 968 (MH+)
[0279]
Example 33
9 β-9,10-O- (4-Benzyloxybutylidene) -13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10 -Deacetyl-9-dihydrobaccatin III
[0280]
Melting point: 102-105 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (6H, s), 1.40 (9H, s), 1.60 (3H, s), 1.64 (3H, s), 1.74-1.97 (5H, m),
2.01-2.43 (4H, m), 2.30 (3H, s), 2.90 (1H, d, J = 4.4Hz), 3.54 (2H, t, J = 6.3Hz),
3.77 (1H, d, J = 6.8Hz), 4.05-4.18 (2H, m), 4.33 (1H, d, J = 8.3Hz),
4.37 (1H, d, J = 8.3Hz), 4.53 (2H, s), 4.59-4.70 (2H, m), 4.88 (1H, t, J = 5.4Hz),
5.10 (1H, s like), 5.18 (1H, d, J = 6.8Hz), 5.30 (1H, br d, J = 9.5Hz),
5.64 (1H, br d, J = 9.5Hz), 6.02-6.14 (2H, m), 7.22-7.43 (10H, m),
7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
FAB mass ： 970 (MH+)
[0281]
Example 34
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- (4 -Morpholinobylidene) Baccatin III
[0282]
Melting point: 128-131 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.40 (9H, s), 1.53-1.74 (2H, m), 1.60 (3H, s), 1.65 (6H, s),
1.81-1.93 (3H, m), 2.03-2.56 (9H, m), 2.30 (3H, s), 2.90 (1H, d, J = 4.4Hz),
3.74 (4H, m), 3.78 (1H, d, J = 6.9Hz), 4.05-4.12 (1H, br),
4.32 (1H, d, J = 8.8Hz), 4.37 (1H, d, J = 8.8Hz), 4.59-4.68 (2H, m),
4.87 (1H, t, J = 5.3Hz), 5.10 (1H, s like), 5.18 (1H, d, J = 6.9Hz),
5.28 (1H, br d, J = 9.2Hz), 5.63 (1H, br d, J = 9.2Hz), 6.05 (1H, d, J = 4.4Hz),
6.08 (1H, t, J = 8.3Hz), 7.23-7.43 (5H, m), 7.47 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
FAB mass ： 949 (MH+)
[0283]
Example 35
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-9-dihydro-9,10- O- (4-morpholinobylidene) baccatin III
[0284]
Melting point: 127-130 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.41 (9H, s), 1.54-1.95 (m), 1.61 (3H, s), 1.65 (3H, s),
1.70 (3H, s), 2.05-2.26 (3H, m), 2.35 (3H, s), 2.30-2.57 (6H, m),
2.93 (1H, d, J = 5.3Hz), 3.74 (4H, t, J = 4.4Hz), 3.81 (1H, d, J = 7.4Hz),
4.07 (1H, br), 4.32 (1H, d, J = 8.3Hz), 4.39 (1H, d, J = 8.3Hz), 4.65 (1H, br),
4.71 (1H, s), 4.87 (1H, t, J = 5.4Hz), 5.10 (1H, s like), 5.20 (1H, d, J = 7.4Hz),
5.32-5.43 (2H, m), 6.05 (1H, d, J = 5.3Hz), 6.10 (1H, t, J = 6.8Hz),
6.318 (1H, d, J = 2.9Hz), 6.36 (1H, dd, J = 2.9Hz, J = 1.9Hz),
7.39 (1H, d, J = 1.9Hz), 7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.11 (2H, d, J = 7.8H).
FAB mass ： 939 (MH+)
[0285]
Example 36
9 β-9,10-O- (2-Benzylaminoethylidene) -4-O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) ) -2-Hydroxypropionyl] -4,10-dideacetyl-9-dihydrobaccatin III
[0286]
Melting point: 111-115 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.01 (3H, t, J = 7.3Hz), 1.27 (3H, s), 1.40 (9H, s), 1.58 (3H, s), 1.63 (3H, s),
1.70 (3H, s), 1.74-2.70 (12H, m), 2.93 (1H, d, J = 4.4Hz),
2.98 (1H, d, J = 4.9Hz), 3.85 (1H, d, J = 7.8Hz), 3.89 (2H, s), 4.07 (1H, s like),
4.31 (1H, d, J = 8.3Hz), 4.38 (1H, d, J = 8.3Hz), 4.69 (1H, d, J = 1.9Hz),
5.01 (1H, t, J = 5.4Hz), 5.05 (1H, s like), 5.22 (1H, d, J = 7.8Hz),
5.31 (1H, br d, J = 9.8Hz), 5.37 (1H, br d, J = 9.8Hz), 6.02 (1H, d, J = 4.4Hz),
6.08 (1H, br t, J = 7.8Hz), 6.32 (1H, d, J = 3.4Hz),
6.36 (1H, dd, J = 3.4Hz, J = 1.9Hz), 7.20-8.41 (6H, m), 7.47 (2H, t, J = 7.3Hz),
7.60 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
FAB mass ： 959 (MH+)
[0287]
Example 37
9 β-4-O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl- 9-Dihydro-9,10-O- (2-dimethylaminoethylidene) baccatin III
[0288]
Melting point: 125-128 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.01 (3H, t, J = 6.8Hz), 1.28 (3H, s), 1.40 (9H, s), 1.55-1.93 (4H, m),
1.61 (3H, s), 1.67 (3H, s), 1.70 (3H, s), 2.10-2.26 (3H, m), 2.38 (6H, s),
2.30-2.70 (3H, m), 2.71 (1H, dd, J = 12.8Hz, J = 6.0Hz),
2.80 (1H, dd, J = 12.8Hz, J = 3.6Hz), 2.93 (1H, d, J = 4.9Hz),
3.82 (1H, d, J = 7.3Hz), 4.08 (1H, br), 4.32 (1H, d, J = 8.3Hz),
4.39 (1H, d, J = 8.3Hz), 4.70 (1H, s), 5.01 (1H, t like, J = 3.9Hz),
5.05 (1H, s like), 5.21 (1H, d, J = 7.3Hz), 5.33 (2H, br s),
6.05 (1H, d, J = 4.9Hz), 6.08 (1H, br t, J = 8.0Hz), 6.33 (1H, d, J = 3.4Hz),
6.36 (1H, dd, J = 3.4Hz, J = 1.9Hz), 7.39 (1H, d, J = 1.9Hz), 7.47 (2H, t, J = 7.3Hz),
7.61 (1H, d, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
FAB mass ： 897 (MH+)
[0289]
Example 38
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- (3 -Butenylidene) Baccatin III
[0290]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.40 (9H, br), 1.43 (3H, s), 1.62 (3H, s), 1.66 (3H, s),
1.89 (1H, s), 2.01-2.44 (4H, m), 2.30 (3H, s), 2.58 (2H, t, J = 6.3Hz),
2.91 (1H, d, J = 4.4Hz), 3.80 (1H, d, J = 7.3Hz), 4.10 (1H, br),
4.33 (1H, d, J = 8.8Hz), 4.38 (1H, d, J = 8.8Hz), 4.58-4.71 (2H, m),
4.89 (1H, t, J = 5.3Hz), 5.08-5.35 (5H, m), 5.63 (1H, br d, J = 10.0Hz),
5.81-5.93 (1H, m), 6.03-6.13 (2H, m), 7.20-7.53 (7H, m),
7.60 (1H, t, J = 7.3Hz), 8.11 (2H, d, J = 7.3Hz).
[0291]
Example 39
9 β-4-O-butanoyl-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -4,10-dideacetyl- 9-Dihydro-9,10-O-isopropylidenebaccatin III
[0292]
Melting point: 108-109 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm):
1.03 (3H, t, J = 6.8Hz), 1.24 (3H, s), 1.40 (3H, s), 1.42 (9H, s),
1.58 (3H, s), 1.62 (3H, s), 1.63 (3H, s), 1.66 (3H, s),
1.84 (2H, q, J = 6.8Hz), 2.10-2.37 (5H, m), 2.54 (2H, m),
2.90 (1H, d, J = 4.4Hz), 3.85 (1H, d, J = 6.8Hz), 4.09 (1H, br),
4.37 (2H, s like), 4.62 (1H, s), 4.70 (1H, d, J = 8.3Hz), 5.06 (1H, s),
5.29 (1H, d, J = 8.8Hz), 5.51 (1H, d, J = 6.8Hz), 5.52 (1H, d, J = 8.8Hz),
6.07 (2H, br), 7.37 (2H, d, J = 5.4Hz), 7.47 (1H, t, J = 7.8Hz),
7.61 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.3Hz), 8.60 (2H, d, 5.9Hz).
FAB mass ： 879 (M+).
[0293]
Example 40
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- [2 -(N-thiazolidino) ethylidene] baccatin III
[0294]
Melting point: 114-117 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.40 (9H, s), 1.57 (3H, s), 1.62 (3H, br), 1.65 (3H, s),
1.90 (1H, s), 2.02-2.45 (4H, m), 2.32 (3H, s), 2.75-3.24 (7H, m),
3.80 (1H, d, J = 7.3Hz), 4.31 (1H, d, J = 8.3Hz), 4.37 (1H, d, J = 8.3Hz),
4.60-4.70 (2H, m), 5.05 (1H, t, J = 4.3Hz), 5.10 (1H, s), 5.23 (1H, d, J = 6.8Hz),
5.29 (1H, d, J = 9.0Hz), 5.62 (1H, d, J = 9.0Hz), 6.00-6.14 (2H, m),
7.24-7.46 (5H, m), 7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.10 (2H, d, J = 7.8Hz).
FAB mass ： 923 (MH+)
[0295]
Example 41
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- [2 -(4-Pyridylmethylamino) ethylidene] baccatin III
[0296]
Melting point: 138-141 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.40 (9H, s), 1.58 (3H, s), 1.63 (6H, s), 1.90 (1H, s),
2.01-2.43 (4H, m), 2.30 (3H, s), 2.89 (1H, d, J = 4.9Hz), 2.99 (1H, d, J = 4.9Hz),
3.82 (1H, d, J = 7.3Hz), 3.91 (1H, s), 4.08 (1H, br), 4.31 (1H, d, J = 8.8Hz),
4.38 (1h, d, J = 8.8Hz), 4.58-4.74 (2H, m), 5.00 (1H, t, J = 4.9Hz), 5.10 (1H, s),
5.23 (1H, d, J = 7.3Hz), 5.28 (1H, d, J = 9.7Hz), 5.61 (1H, d, J = 9.7Hz),
6.03 (1H, d, J = 4.9Hz), 6.10 (1H, t, J = 7.9Hz), 7.21-7.51 (9H, m),
7.61 (1H, t, J = 7.4Hz), 8.10 (2H, d, J = 7.4Hz), 8.56 (2H, d, J = 5.9Hz).
FAB mass ： 942 (MH+)
[0297]
Example 42
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- [2 -(2-morpholinoethylamino) ethylidene] baccatin III
[0298]
Melting point: 124-127 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.40 (9H, s), 1.57 (3H, s), 1.60 (3H, s), 1.65 (3H, s),
2.02-2.60 (12H, m), 2.30 (3H, s), 2.75-2.87 (2H, m), 2.90 (2H, d, J = 4.9Hz),
2.99 (1H, d, J = 4.9Hz), 3.72 (4H, t, J = 4.4Hz), 3.81 (1H, d, J = 7.3Hz),
4.08 (1H, s), 4.32 (1H, d, J = 8.3Hz), 4.37 (1H, d, J = 8.3Hz), 4.62 (1H, s),
4.98 (1H, t, J = 4.9Hz), 5.10 (1H, s), 5.22 (1H, d, J = 7.3Hz),
5.29 (1H, br d, J = 9.3Hz), 5.62 (1H, br d, J = 9.3Hz), 6.04 (1H, d, J = 4.9Hz),
6.09 (1H, t, J = 7.3Hz), 7.18-7.52 (7H, m), 7.60 (1H, t, J = 7.4Hz),
8.10 (2H, d, J = 7.4Hz).
FAB mass ： 964 (MH+)
[0299]
Example 43
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -9,10- O- [2- (cyclopropylamino) ethylidene] -10-Acetyl-9-dihydrobaccatin III
[0300]
Melting point: 139-142 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.35-0.54 (4H, m), 1.26 (3H, s), 1.40 (9H, s), 1.57 (3H, s), 1.61 (3H, s),
1.68 (3H, s), 1.89 (1H, br), 2.02-2.44 (5H, m), 2.30 (3H, s),
2.90 (1H, d, J = 4.9Hz), 3.05 (2H, d, J = 5.3Hz), 3.80 (1H, d, J = 7.4Hz),
4.10 (1H, s), 4.32 (1H, d, J = 8.3Hz), 4.38 (1H, d, J = 8.3Hz), 4.62 (1H, s),
4.96 (1H, t, J = 5.3Hz), 5.10 (1H, s), 5.21 (1H, d, J = 7.4Hz),
5.29 (1H, br d, J = 8.8Hz), 5.62 (1H, br d, J = 8.8Hz), 6.00-6.12 (2H, m),
7.19-7.52 (5H, m), 7.60 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
FAB mass ： 891 (MH+)
[0301]
Example 44
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9,10-O- [2- (diethylamino) Ethylidene] -9-dihydrobaccatin III
[0302]
Melting point: 132-135 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.08 (6H, t, J = 7.3Hz), 1.25 (3H, s), 1.40 (9H, s), 1.60 (3H, s), 1.62 (3H, s),
1.67 (3H, s), 1.88 (1H, s), 1.99-2.43 (4H, m), 2.29 (3H, s),
2.60-2.73 (4H, m), 2.80-2.93 (2H, m), 2.89 (1H, d, J = 4.9Hz),
3.77 (1H, d, J = 6.8Hz), 4.10 (1H, br), 4.32 (1H, d, J = 8.8Hz),
4.37 (1H, d, J = 8.8Hz), 4.58-4.69 (2H, m), 4.97 (1H, br), 5.10 (1H, s),
5.20 (1H, d, J = 6.8Hz), 5.29 (1H, d, J = 8.8Hz), 5.62 (1H, d, J = 8.8Hz),
6.01-6.12 (2H, m), 7.24-7.52 (7H, m), 7.60 (1H, t, J = 7.3Hz),
8.10 (2H, d, J = 7.3Hz).
FAB mass ： 907 (MH+)
[0303]
Example 45
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-9-dihydro-9,10-O- [2 -(2-Hydroxyethylamino) ethylidene] baccatin III
[0304]
Melting point: 149-151 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.40 (9H, s), 1.57 (3H, s), 1.60 (3H, s), 1.64 (3H, s),
1.89-2.47 (m), 2.30 (3H, s), 2.83-2.96 (3H, m), 3.00 (2H, d, J = 4.9Hz),
3.67 (2H, t, J = 4.9Hz), 3.81 (1H, d, J = 7.3Hz), 4.08 (1H, s),
4.31 (1H, d, J = 8.8Hz), 4.37 (1H, d, J = 8.8Hz), 4.62 (1H, s),
4.97 (1H, t, J = 4.9Hz), 5.10 (1H, s), 5.22 (1H, d, J = 7.3Hz),
5.28 (1H, d, J = 9.8Hz), 5.64 (1H, d, J = 9.8Hz), 6.04 (1H, d, J = 4.9Hz),
7.21-7.51 (7H, m), 7.60 (1H, t, J = 7.3Hz), 8.10 (2H, d, J = 7.3Hz).
FAB mass ： 895 (MH+)
[0305]
Example 46
9 β-9,10-O- [2- (N-aziridino) ethylidene] -13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-Deacetyl-9-dihydrobaccatin III
[0306]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.35 (3H, s), 1.42 (9H, s), 1.53 (3H, s), 1.68 (3H, s), 1.78 (3H, s),
1.70-2.00 (2H, m), 2.12-2.48 (6H, m), 2.42 (3H, s), 2.48-2.58 (1H, m),
2.64-2.73 (1H, m), 2.96 (1H, d, J = 4.5Hz), 3.86 (1H, d, J = 7.0Hz),
4.03-4.11 (1H, m), 4.31 (1H, d, J = 8.3Hz), 4.41 (1H, d, J = 8.3Hz),
4.65 (1H, d, J = 8.5Hz), 5.03-5.32 (4H, m), 5.40-5.55 (2H, m),
6.01 (1H, d, J = 4.5Hz), 6.14-6.25 (2H, m), 7.20-7.45 (5H, m),
7.49 (2H, t, J = 7.5Hz), 7.60 (1H, t, J = 7.5Hz), 8.14 (2H, d, J = 7.5Hz).
FAB mass ： 859 (MH+-H2O)
[0307]
Example 47
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -10-deacetyl-9-dihydro-9,10-O- (Isopropylidene) Baccatin III
[0308]
Melting point: 170-174 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (s), 1.37 (9H, s), 1.40 (s), 1.43 (s), 1.58 (s), 1.63 (s), 1.68 (s),
2.05 (1H, m), 2.09 (1H, m), 2.21 (1H, m), 2.25 (1H, m), 2.47 (3H, s),
2.90 (1H, d, J = 4Hz), 3.77 (1H, d, J = 7Hz), 4.08 (1H, br), 4.32 (1H, br),
4.38 (2H, s), 4.69 (1H, d, J = 8.5Hz), 5.00 (1H, d, J = 10Hz), 5.11 (1H, br),
5.48 (1H, d, J = 7Hz), 5.78 (1H, d, J = 10Hz), 6.05 (1H, d, J = 4Hz), 6.23 (1H, t),
7.36 (2H, s-d), 7.48 (2H, t, J = 7.5Hz), 7.61 (1H, t, J = 7.5Hz),
8.12 (2H, d, J = 7.5Hz), 8.59 (2H, s-d).
FAB mass ： 865 (M+)
[0309]
Example 48
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -4,10-dideacetyl-9-dihydro-9, 10-O-isopropylidene-4-O-propionylbaccatin III
[0310]
Melting point: 140-147 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm):
1.25 (3H, s), 1.33 (3H, t, J = 7.8Hz), 1.41 (9H, s), 1.42 (3H, s),
1.53 (3H, s), 1.63 (3H, s), 1.66 (6H, s), 2.07-2.36 (4H, m),
2.40-2.57 (2H, m), 2.91 (1H, d, J = 4.9Hz), 3.80 (1H, d, J = 7.3Hz),
4.08 (1H, br), 4.38 (2H, AB type q, J = 15.6Hz), 4.62 (1H, s),
4.72 (1H, d, J = 7.9Hz), 5.04 (1H, s), 5.28 (1H, d, J = 8.5Hz),
5.52 (1H, d, J = 7.3Hz), 5.70 (1H, d, J = 8.5Hz), 6.07 (2H, br),
7.36 (2H, s), 7.47 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.3Hz),
8.13 (2H, d, J = 7.3Hz), 8.60 (2H, br).
FAB mass ： 865 (M+).
[0311]
Example 49
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-9-dihydro-9,10-O- (2-propenylidene) baccatin III
[0312]
Melting point: 225-228 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.04-1.16 (2H, m), 1.27 (3H, s), 1.41 (9H, s), 1.60 (3H, s),
1.60-1.75 (2H, m), 1.68 (3H, s), 1.74 (3H, s), 1.92 (1H, s),
2.03-2.32 (3H, m), 2.41 (1H, dd, J = 14.0Hz, J = 9.6Hz), 2.92 (1H.d.J = 4.4Hz),
3.88 (1H, d, J = 7.3Hz), 3.96-4.14 (2H, m), 4.27 (1H, d, J = 8.8Hz),
4.33 (1H, d, J = 8.8Hz), 4.56 (1H, d, J = 7.8Hz), 4.71 (1H, s like),
5.05 (1H, s like), 5.22 (1H, d, J = 5.8Hz), 5.28 (1H, d, J = 7.3Hz),
5.37 (2H, s like), 5.45 (1H, d, J = 10.3Hz), 5.56 (1H, d, J = 17.1Hz),
5.97-6.15 (3H, m), 6.27-6.40 (2H, m), 7.36 (1H, s like),
7.48 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz), 8.05 (2H, d, J = 7.8Hz).
FAB mass ： 864 (MH+)
[0313]
Example 50
9 β-9,10-O- (2-Aminoethylidene) -13- O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl -9-Dihydrobaccatin III
[0314]
Melting point: 155-158 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.40 (9H, s), 1.58 (3H, s), 1.60 (3H, s), 1.65 (3H, s),
2.00-2.44 (4H, m), 2.30 (3H, s), 2.90 (1H, d, J = 4.9Hz), 3.02 (2H, d, J = 4.4Hz),
3.82 (1H, d, J = 7.4Hz), 4.09 (1H, s like), 4.32 (1H, d, J = 8.3Hz),
4.37 (1H, d, J = 8.3Hz), 4.62 (1H, s like), 4.84 (1H, t, J = 4.9Hz), 5.10 (1H, s),
5.23 (1H, d, J = 7.4Hz), 5.28 (1H, d, J = 9.2Hz), 5.62 (1H, d, J = 9.2Hz),
6.04 (1H, d, J = 4.9Hz), 6.08 (1H, t, J = 8.3Hz), 7.20-7.56 (7H, m),
7.47 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
FAB mass ： 851 (MH+)
[0315]
Example 51
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-9-dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0316]
Melting point: 147-148 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.01-1.19 (2H, m), 1.27 (3H, s), 1.41 (9H, s), 1.58 (3H, s), 1.65 (3H, s),
1.72 (3H, s), 1.92 (1H, s), 2.04-2.32 (3H, m),
2.40 (1H, dd, J = 15.1Hz, J = 9.2Hz), 2.52-2.70 (4H, m),
2.74 (1H, dd, J = 13.1Hz, J = 4.8Hz), 2.90 (1H, d, J = 4.9Hz),
3.73 (4H, t like, J = 4.9Hz), 3.81 (1H, d, J = 6.8Hz), 4.06 (1H, br),
4.26 (1H, d, J = 8.8Hz), 4.33 (1H, d, J = 8.8Hz), 4.66 (1H, d, J = 8.3Hz),
4.71 (1H, s), 4.89-5.09 (2H, m), 5.21 (1H, d, J = 7.4Hz), 5.37 (2H, m),
6.01-6.10 (2H, m), 6.29-6.39 (2H, m), 7.36 (1H, s like),
7.48 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz), 8.05 (2H, d, J = 7.8Hz).
FAB mass ： 937 (MH+)
[0317]
Example 52
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl-9- Dihydro-9,10-O- (2-propenylidene) baccatin III
[0318]
Melting point: 218-220 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.00-1.10 (2H, m), 1.20-1.45 (2H, m), 1.25 (3H, s), 1.40 (3H, s),
1.50-1.80 (2H, m), 1.58 (3H, s), 1.95 (1H, s), 2.07-2.24 (3H, m),
2.41 (1H, dd, J = 15.1Hz, J = 9.8Hz), 2.88 (1H, d, J = 3.9Hz),
3.86 (1H, d, J = 6.9Hz), 4.08 (1H, br), 4.26 (1H, d, J = 8.7Hz),
4.31 (1H, d, J = 8.7Hz), 4.53 (1H, br d, J = 7.9Hz), 5.04 (1H, s),
5.21 (1H, d, J = 6.3Hz), 5.25-5.33 (2H, m), 5.44 (1H, d, J = 10.7Hz),
5.56 (11H, d, J = 17.0Hz), 5.609 (1H, d, J = 8.8Hz), 5.96-6.12 (3H, m),
7.24-7.51 (7H, m), 7.60 (1H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz),
8.03 (2H, d, J = 7.3Hz).
FAB mass ： 874 (MH+)
[0319]
Example 53
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl-9- Dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0320]
Melting point: 146-147 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.96-1.02 (2H, m), 1.24 (3H, s), 1.18-1.40 (2H, m), 1.40 (9H, s),
1.57 (6H, s), 1.64 (3H, s), 1.90-2.15 (4H, m), 2.30-2.98 (8H, m),
3.61-3.83 (5H, m), 4.06 (1H, br), 4.26 (1H, d, J = 8.3Hz),
4.31 (1H, d, J = 8.3Hz), 4.50-4.74 (2H, m), 4.92-5.03 (2H, m),
5.20 (1H, d, J = 6.4Hz), 5.27 (1H, d, J = 9.3Hz), 5.68 (1H, d, J = 9.3Hz),
5.89-6.15 (2H, m), 7.17-7.52 (7H, m), 7.60 (1H, t, J = 7.3Hz),
8.03 (2H, d, J = 7.3Hz).
FAB mass ： 947 (MH+)
[0321]
Example 54
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -4-O-butanoyl-4,10-dideacetyl-9- Dihydro-9,10-O-isopropylidene hackatin III
[0322]
Melting point: 160-163 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm):
1.11 (3H, t, J = 7.5Hz), 1.29 (s), 1.37 (9H, s), 1.40 (s), 1.42 (s), 1.58 (s),
1.64 (s), 1.67 (s), 1.92 (1H, m), 2.07 (2H, m), 2.24 (2H, m), 2.56 (1H, m),
2.71 (1H, m), 2.92 (1H, s-d), 3.77 (1H, d, J = 7Hz), 4.08 (1H, br),
4.30 (1H, br), 4.38 (2H, s), 4.71 (1H, d, J = 8Hz), 5.00 (1H, d, J = 10Hz),
5.06 (1H, br), 5.48 (1H, d, J = 7Hz), 5.80 (1H, d, J = 10Hz), 6.06 (1H, s-d),
6.20 (1H, t-br), 7.37 (2H, d, J = 5Hz), 7.48 (2H, t, J = 7.5Hz),
7.61 (1H, t, J = 7.5Hz), 8.14 (2H, d, J = 7.5Hz), 8.59 (2H, d, J = 5Hz).
FAB mass ： 893 (M+)
[0323]
Example 55
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
[0324]
Melting point: 128-134 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm):
1.23 (3H, s), 1.26 (4H, s), 1.41 (3H, s), 1.42 (3H, s), 1.48 (9H, s),
1.53 (3H, s), 1.60 (3H, s), 1.66 (3H, s), 1.92-2.37 (5H, m),
2.88 (1H, d, J = 5.3Hz), 3.76 (1H, d, J = 7.3Hz), 4.06 (1H, m),
4.30 (2H, s), 4.60 (1H, br), 4.68 (1H, d, J = 8.3Hz), 5.06 (1H, s),
5.27 (1H, d, J = 8.0Hz), 5.54 (1H, d, J = 7.3Hz), 5.89 (1H, d, J = 8.0Hz),
6.01 (1H, t, J = 7.3Hz), 6.08 (1H, d, J = 5.3Hz), 7.37 (2H, br),
7.48 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.3Hz), 8.03 (2H, d, J = 7.3Hz),
8.59 (2H, br).
FAB mass ： 877 (MH+).
[0325]
Example 56
9 β-13-O- [3- (tert-Butoxycarbonylamino) -3- (2-furyl) -2-hydroxy-2-methylpropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl- 9-Dihydro-9,10-O- (2-propenylidene) baccatin III
[0326]
Melting point: 230-233 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.20-1.80 (4H, m), 1.31 (3H, s), 1.37 (9H, s), 1.45 (3H, s), 1.60 (3H, s),
1.69 (3H, s), 1.89-2.02 (2H, m), 2.92 (1H, d, J = 3.9Hz), 3.86 (1H, d, J = 7.3Hz),
4.05-4.13 (1H, m), 4.22 (1H, br s), 4.29 (1H, d, J = 8.3Hz),
4.33 (1H, d, J = 8.3Hz), 4.61 (1H, d, J = 7.9Hz), 5.07 (1H, s like),
5.16-5.29 (3H, m), 5.44 (1H, d, J = 10.8Hz), 5.50 (1H, d, J = 9.7Hz),
5.56 (1H, d, J = 17.1Hz), 5.98-6.10 (1H, m), 6.08 (1H, d, J = 3.9Hz),
6.20 (1H, t, J = 8.0Hz), 6.30 (1H, d, J = 3.5Hz), 6.35 (1H, m), 7.36 (1H, s like),
7.49 (2H, t, J = 7.4Hz), 7.61 (1H, t, J = 7.4Hz), 8.06 (2H, d, J = 7.4Hz).
FAB mass ： 878 (MH+)
[0327]
Example 57
9 β-13-O- [3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxy-2-methylpropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl- 9-Dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0328]
Melting point: 140-143 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.10-1.82 (4H, m), 1.31 (3H, s), 1.37 (9H, s), 1.58 (3H, s), 1.66 (6H, s),
1.67 (3H, s), 1.90-2.03 (1H, m), 1.92 (1H, s), 2.04-2.36 (4H, m),
2.50-2.70 (4H, m), 2.74 (1H, dd, J = 13.6Hz, J = 5.3Hz),
2.82 (1H, dd, J = 13.6Hz, J = 3.4Hz), 2.90 (1H, d, J = 3.9Hz),
3.73 (4H, t, J = 4.8Hz), 3.78 (1H, d, J = 7.3Hz), 4.02-4.10 (1H, m),
4.18 (1H, br), 4.28 (1H, d, J = 8.8Hz), 4.34 (1H, d, J = 8.8Hz),
4.69 (1H, d, J = 8.3Hz), 5.02 (1H, t, J = 4.9Hz), 5.07 (1H, s), 5.15-5.26 (2H, m),
5.48 (1H, d, J = 9.8Hz), 6.06 (1H, d, J = 3.9Hz), 6.19 (1H, t, J = 8.3Hz),
6.30 (1H, d, J = 3.0Hz), 6.35 (1H, dd, J = 3.0Hz, J = 2.9Hz), 7.36 (1H, d, J = 2.9Hz),
7.49 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.8Hz), 8.06 (2H, d, J = 7.8Hz).
FAB mass ： 951 (MH+)
[0329]
Example 58
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-9-dihydro-9,10-O- (2-propenylidene) baccatin III
[0330]
Melting point: 156-157 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.04-1.16 (2H, m), 1.20-1.80 (2H, m), 1.23 (3H, s), 1.41 (9H, s),
1.63 (6H, s), 1.67 (3H, s), 1.95-2.28 (4H, m), 2.36-2.47 (1H, m),
2.87 (1H, d, J = 4.4Hz), 3.85 (1H, d, J = 7.2Hz), 4.08 (1H.br),
4.27 (1H, d, J = 8.8Hz), 4.30 (1H, d, J = 8.8Hz), 4.47-4.65 (2H, m),
5.05 (1H, s like), 5.21 (1H, d, J = 5.8Hz), 5.23-5.34 (2H, m),
5.45 (1H, d, J = 10.3Hz), 5.56 (1H, d, J = 17.2Hz), 5.79 (1H, d, J = 9.8Hz),
6.00-6.12 (3H, m), 7.35 (2H, d, J = 5.8Hz), 7.47 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.02 (2H, d, J = 7.8Hz), 8.57 (2H, d, J = 5.8Hz).
FAB mass ： 875 (MH+)
[0331]
Example 59
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy- (4-pyridyl) propionyl] -10-deacetyl-7-deoxy-9-dihydro-9, 10-O-isopropylidenebaccatin III
[0332]
Melting point: 162.5-167.5 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23 (3H, s), 1.43 (9H, s), 1.51 (3H, s), 1.55 (3H, s), 1.57 (3H, s),
1.61 (3H, s), 1.71 (3H, s), 1.60-2.10 (5H, m), 1.97 (1H, s), 2.28 (3H, s),
2.34 (1H, dd, J = 10.2, J = 15.1Hz), 2.91 (1H, d, J = 4.9Hz), 4.12 (1H, d, J = 7.1Hz),
4.27 (1H, d, J = 8.3Hz), 4.32 (1H, d, J = 8.3Hz), 4.63 (1H, br s),
4.82 (1H, br s), 4.93 (1H, br s), 5.30 (1H, d, J = 9.1Hz),
5.56 (1H, d, J = 7.1Hz), 5.81 (1H, d, J = 9.1Hz), 6.00 (1H, d, J = 4.9Hz),
6.09 (1H, br t, J = 7.8Hz), 7.36 (2H, d, J = 5.9Hz), 7.47 (2H, t, J = 7.3Hz),
7.60 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz), 8.59 (2H, d, J = 5.9Hz)
[0333]
Example 60
9 β-13-O- [3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl- 9-Dihydro-9,10-O-isopropylidenebaccatin III
[0334]
Melting point: 152-158 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm):
1.16 (4H, m), 1.28 (3H, s), 1.39 (9H, s), 1.40 (3H, s), 1.42 (3H, s),
1.58 (3H, s), 1.60 (3H, s), 1.67 (3H, s), 1.83-2.36 (5H, m),
2.89 (1H, d, J = 3.9Hz), 3.74 (1H, d, J = 7.3Hz), 4.07 (1H, m),
4.32 (2H, s), 4.70 (1H, d, J = 8.3Hz), 5.00 (1H, d, J = 10.3Hz),
5.07 (1H, s), 5.49 (1H, d, J = 6.8Hz), 5.87 (1H, d, J = 9.8Hz),
6.08 (1H, d, J = 4.4Hz), 6.20 (1H, m), 7.38 (2H, d, J = 5.9Hz),
7.49 (2H, t, J = 7.8Hz), 7.62 (1H, t, J = 7.3Hz), 8.04 (2H, d, J = 7.3Hz),
8.57 (2H, d, J = 5.4Hz).
FAB mass ： 891 (MH+).
[0335]
Example 61
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl-7- Deoxy-9-dihydro-9,10-O- (2-propenylidene) baccatin III
[0336]
Melting point: 130-133 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.00-1.10 (2H, m), 1.20-1.40 (2H, m), 1.24 (3H, s), 1.41 (9H, s),
1.45 (3H, s), 1.62 (3H, s), 1.62-2.10 (6H, m), 2.01 (3H, s),
2.38 (1H, dd, J = 14.7Hz, J = 8.8Hz), 2.89 (1H, d, J = 4.4Hz),
4.14 (1H, d, J = 7.0Hz), 4.18 (1H, d, J = 8.8Hz), 4.27 (1H, d, J = 8.8Hz),
4.60 (1H, br s) .4.65 (1H, br s), 4.87 (1H, s), 5.23 (1H, d, J = 5.9Hz),
5.20-5.20 (1H, m), 5.29 (1H, d, J = 5.9Hz), 5.46 (1H, d, J = 10.7Hz),
5.57 (1H, d, J = 17.6Hz), 5.74 (1H, d, J = 9.8Hz), 5.95-6.08 (3H, m),
7.29 (1H, d, J = 7.3Hz), 7.34 (2H, t, J = 7.3Hz), 7.42 (2H, d, J = 7.3Hz),
7.47 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz), 8.04 (2H, d, J = 7.3Hz).
FAB mass ： 858 (MH+)
[0337]
Example 62
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-7-deoxy-9-dihydro-9,10-O- (2-propenylidene) baccatin III
[0338]
Melting point: 132-135 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.03-1.13 (2H, m), 1.25 (3H, s), 1.30-1.50 (2H, m), 1.41 (9H, s),
1.46 (3H, s), 1.63 (3H, s), 1.71-1.95 (5H, m), 1.78 (3H, br s),
2.01-2.21 (2H, m), 2.40 (1H, dd, J = 15.1Hz, J = 9.8Hz), 2.91 (1H, d, J = 4.9Hz),
4.14-4.22 (2H, m), 4.29 (1H, d, J = 8.3Hz), 4.33 (1H, br s), 4.71 (1H, s),
4.87 (1H, s), 5.24 (1H, d, J = 6.3Hz), 5.31 (1H, d, J = 6.8Hz),
5.37 (1H, br d, J = 9.8Hz), 5.44 (1H, br d, J = 9.8Hz), 5.46 (1H, d, J = 10.8Hz),
5.57 (1H, d, J = 17.1Hz), 5.93-6.10 (3H, m), 6.31 (1H, d, J = 2.9Hz),
6.34 (1H, dd, J = 2.9Hz, J = 1.9Hz), 7.36 (1H, s like), 7.48 (2H, t, J = 7.4Hz),
7.61 (1H, t, J = 7.43Hz), 8.06 (2H, d, J = 7.4Hz) .FAB mass ： 848 (MH+)
[0339]
Example 63
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl-7- Deoxy-9-dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0340]
Melting point: 118-121 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.00-1.09 (2H, m), 1.24 (3H, s), 1.20-1.40 (2H, m), 1.40 (9H, s),
1.43 (3H, s), 1.50-2.21 (6H, m), 1.55-1.62 (6H, m),
2.39 (1H, dd, J = 14.5Hz, J = 10.2Hz), 2.53-2.82 (5H, m), 2.86 (1H, d, J = 3.9Hz),
3.74 (4H, t, J = 4.9Hz), 4.08 (1H, d, J = 7.3Hz), 4.18 (1H, d, J = 8.8Hz),
4.26 (1H, d, J = 8.8Hz), 4.61 (1H, br), 4.86 (1H, br s),
5.04 (1H, dd, J = 4.4Hz, J = 3.4Hz), 5.23 (1H, d, J = 7.3Hz), 5.29 (1H, d, J = 8.3Hz),
5.73 (1H, d, J = 8.3Hz), 5.95-6.06 (2H, m), 7.21-7.30 (1H,),
7.41 (2H, d, J = 7.3Hz), 7.47 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz),
8.04 (2H, d, J = 7.3Hz).
FAB mass ： 931 (MH+)
[0341]
Example 64
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-7-deoxy-9-dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0342]
Melting point: 129-132 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.02-1.12 (2H, m), 1.26 (3H, s), 1.34-1.49 (2H, m), 1.41 (9H, s),
1.60 (6H, s), 1.70-2.21 (6H, m), 1.76 (3H, s),
2.39 (1H, dd, J = 15.2Hz, J = 9.7Hz), 2.53-2.82 (6H, m), 2.90 (1H, d, J = 4.8Hz),
3.74 (4H, t, J = 4.4Hz), 4.11 (1H, d, J = 7.3Hz), 4.18 (1H, d, J = 8.8Hz),
4.29 (1H, d, J = 8.8Hz), 4.71 (1H, s), 4,86 (1H, br s),
5.04 (1H, t like, J = 5.4Hz), 5.24 (1H, d, J = 7.3Hz), 5.37 (1H, d, J = 8.8Hz),
5.44 (1H, d, J = 8.8Hz), 5.98-6.09 (2H, m), 6.31 (1H, d, J = 2.9Hz),
6.34 (1H, dd, J = 2.9Hz, J = 1.4Hz), 7.36 (1H, d, J = 1.4Hz), 7.48 (2H, t, J = 7.8Hz),
7.61 (1H, t, J = 7.8Hz), 8.06 (2H, d, J = 7.8Hz).
FAB mass ： 921 (MH+)
[0343]
Example 65
9 β-13-O- [3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl- 7-Deoxy-9-dihydro-9,10-O-isopropylidenebaccatin III
[0344]
Melting point: 160-163 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.00-2.30 (11H, m), 1.26 (3H, s), 1.38 (9H, s), 1.42 (3H, s), 1.46 (6H, s),
1.56 (3H, s), 1.61 (6H, s), 2.91 (1H, d, J = 4.0Hz), 4.10 (1H, d, J = 7.3Hz),
4.22 (1H, d, J = 8.8Hz), 4.27 (1H, d, J = 8.8Hz), 4.80-4.90 (2H, m),
5.00 (1H, d, J = 9.8Hz), 5.52 (1H, d, J = 7.3Hz), 5.90 (1H, d, J = 9.8Hz),
6.01 (1H, d, J = 4.0Hz), 6.15-6.25 (1H, m), 7.36 (2H, d, J = 5.3Hz),
7.48 (2H, t, J = 7.3Hz), 7.61 (1H, t, J = 7.3Hz), 8.05 (2H, d, J = 7.3Hz),
8.56 (2H, d, J = 5.3Hz).
FAB mass ： 875 (MH+)
[0345]
Example 66
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (2-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl- 9-Dihydro-9,10-O-isopropylidenebaccatin III
[0346]
Melting point: 151-153 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.15 (4H, m), 1.30 (3H, s), 1.39 (3H, s), 1.42 (9H, s), 1.51 (3H, s),
1.57 (6H, s), 1.63 (3H, s), 1.66 (3H, s), 2.09-2.42 (5H, m),
2.92 (1H, d, J = 4.9Hz), 3.82 (1H, m), 4.04 (1H, m),
4.34 (2H, AB type q, J = 7.8Hz), 4.76 (1H, d, J = 8.3Hz), 5.10 (1H, s),
5.11 (1H, d, J = 10.3Hz), 5.48 (1H, d, J = 7.3Hz), 6.04 (1H, d, J = 4.9Hz),
6.16 (1H, t, J = 8.3Hz), 7.23 (1H, t, J = 4.4Hz), 7.42 (1H, d, J = 7.8Hz),
7.49 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.3Hz), 7.72 (1H, t, J = 6.8Hz),
8.07 (2H, d, J = 7.3Hz), 8.46 (1H, d, J = 4.4Hz).
FAB mass ： 891 (MH+).
[0347]
Example 67
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-7-deoxy-9,10- O-ethylidene-9-dihydrobaccatin III
[0348]
Melting point: 104-106 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.20-2.10 (5H, m), 1.25 (3H, s), 1.42 (9H, s), 1.49 (3H, d, J = 4.8Hz),
1.50 (3H, s), 1.62 (3H, s), 1.74 (3H, s), 2.30-2.50 (1H, m), 2.32 (3H, s),
2.93 (1H, d, J = 4.8Hz), 4.12 (1H, d, J = 7.4Hz), 4.24 (1H, d, J = 8.8Hz),
4.29 (1H, br), 4.33 (1H, d, J = 8.8Hz), 4.72 (1H, d, J = 2.0Hz), 4.92 (1H, s),
5.06 (1H, q, J = 4.8Hz), 5.25 (1H, d, J = 8.3Hz), 5.39 (1H, d, J = 10.0Hz),
5.44 (1H, d, J = 10.0Hz), 6.01 (1H, d, J = 4.8Hz), 6.05-6.20 (1H, m),
6.31 (1H, d, J = 2.9Hz), 6.35 (1H, dd, J = 2.9Hz, J = 1.9Hz), 7.22 (1H, s like),
7.47 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.13 (2H, d, J = 7.8Hz).
FAB mass ： 810 (MH+)
[0349]
Example 68
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-7-deoxy-9-dihydro-9,10- O- (2-propenylidene) baccatin III
[0350]
Melting point: 140-143 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.20-2.20 (5H, m), 1.25 (3H, s), 1.41 (9H, s), 1.48 (3H, s), 1.63 (3H, s),
2.27 (3H, s), 2.37 (1H, dd, J = 15.1Hz, J = 5.3Hz), 2.90 (1H, d, J = 4.4Hz),
4.15 (1H, d, J = 7.3Hz), 4.23 (1H, d, J = 8.3Hz), 4.31 (1H, d, J = 8.3Hz),
4.50 (1H, s like), 4.62 (1H, s like), 4.91 (1H, s), 5.20-5.40 (2H, m),
5.23 (1H, d, J = 5.9Hz), 5.46 (1H, d, J = 10.2Hz), 5.57 (1H, d, J = 17.6Hz),
5.71 (1H, d, J = 9.8Hz), 5.90-6.20 (3H, m), 7.20-7.50 (7H, m),
7.60 (1H, t, J = 7.9Hz), 8.11 (2H, d, J = 7.9Hz). FAB mass ： 832 (MH+)
[0351]
Example 69
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
[0352]
Melting point: 138-141 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23-1.29 (4H, m), 1.27 (3H, s), 1.39 (9H, s), 1.41 (3H, s),
1.58 (3H, s), 1.63 (3H, s), 1.66 (3H, s), 1.74 (3H, s), 1.85 (1H, s),
1.98-2.39 (5H, m), 2.94 (1H, d, J = 4.9Hz), 3.84 (1H, d, J = 7.3Hz),
4.06 (1H, m), 4.30 (2H, AB type q, J = 8.3Hz), 4.55 (1H, br),
4.79 (1H, d, J = 8.3Hz), 4.88 (1H, s), 5.07 (1H, s),
5.34 (1H, d, J = 9.3Hz), 5.55 (1H, d, J = 6.8Hz), 5.83 (1H, d, J = 9.8Hz),
6.05 (2H, m), 7.22 (1H, dd, J = 7.3Hz, J = 4.9Hz), 7.41 (1H, d, J = 7.8Hz),
7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.3Hz), 7.71 (1H, t, J = 6.4Hz),
8.05 (2H, d, J = 6.8Hz), 8.50 (1H, d, J = 4.4Hz).
FAB mass ： 877 (MH+).
[0353]
Example 70
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-7-deoxy-9-dihydro-9,10-O-isopropylidenebaccatin III
[0354]
Melting point: 155-157 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.00-1.20 (2H, m), 1.20-1.50 (2H, m), 1.22 (3H, s), 1.43 (9H, s),
1.47 (3H, s), 1.50-2.10 (6H, m), 1.56 (6H, s), 1.60 (6H, s),
2.35 (1H, t like, J-10.8Hz), 2.87 (1H, d, J = 4.4Hz), 4.11 (1H, d, J = 7.4Hz),
4.20 (1H, d, J = 8.8Hz), 4.27 (1H, d, J = 8,8Hz), 4.59 (1H, s), 4.87 (1H, s),
5.28 (1H, d, J = 8.8Hz), 5.56 (1H, d, J = 7.4Hz), 5.84 (1H, d, J = 8.8Hz),
5.95-6.10 (2H, m), 7.36 (2H, d, J = 5.9Hz), 7.47 (2H, t, J = 7.8Hz),
7.61 (1H, t, J = 7.8Hz), 8.04 (2H, d, J = 7.8Hz), 8.58 (2H, d, J = 5.9Hz).
FAB mass ： 861 (MH+)
[0355]
Example 71
7 α, 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-7-deoxy-9-dihydro-7- Fluoro-9,10-O- (2-morpholinoethylidene) baccatin III
[0356]
Melting point: 139-142.5 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.17 (3H, s), 1.40 (9H, s), 1.58 (3H, s), 1.63 (6H, s), 1.82 (1H, s),
2.08-2.35 (2H, m), 2.28 (3H, s), 2.37 (1H, dd, J = 9.8, J = 15.1Hz),
2.40-2.55 (1H, m), 2.55-2.67 (4H, m), 2.85 (1H, dd, J = 4.4, J = 13.7Hz),
2.89 (1H, dd, J = 4.4, J = 13.7Hz), 3.48 (1H, d, J = 5.2Hz), 3.74 (4H, t, J = 4.6Hz),
4.10-4.28 (1H, br), 4.18 (1H, d, J = 8.3Hz), 4.25 (1H, d, J = 8.3Hz),
4.38 (1H, d, J = 8.3Hz), 4.61 (1H, br s), 4.75 (1H, br d, J = 46.4Hz),
4.91 (1H, t, J = 4.4Hz), 4.95 (1H, br d, J = 5.9Hz), 5.31 (1H, br d, J = 9.1Hz),
5.37 (1H, d, J = 8.3Hz), 5.66 (1H, br d, J = 9.1Hz), 5.90 (1H, d, J = 5.2Hz),
6.07 (1H, br t, J = 8.3Hz), 7.28 (1H, t, J = 7.3Hz), 7.35 (2H, t, J = 7.3Hz),
7.41 (2H, d, J = 7.3Hz), 7.48 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.8Hz),
8.09 (2H, d, J = 7.8Hz)
FAB mass: 923 (MH+)
[0357]
Example 72
7 α, 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -10-deacetyl-7-deoxy-9- Dihydro-7-fluoro-9,10-O-isopropylidenebaccatin III
[0358]
Melting point: 154-158 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.19 (3H, s), 1.41 (9H, s), 1.42 (3H, s), 1.56 (3H, s), 1.61 (3H, s),
1.62 (3H, s), 1.63 (3H, s), 1.87 (1H, s), 2.32 (3H, s), 2.08-2.47 (4H, m),
3.46 (1H, d, J = 5.4Hz), 4.28-4.40 (1H, br), 4.31 (1H, d, J = 8.5Hz),
4.36 (1H, d, J = 8.5Hz), 4.59 (1H, d, J = 8.6Hz), 4.63 (1H, br s),
4.87 (1H, ddd, J = 3.9, J = 7.8, J = 45.9Hz), 4.93-4.97 (1H, m),
5.31 (1H, br d, J = 9.6Hz), 5.52 (1H, d, J = 8.6Hz), 5.69 (1H, br d, J = 9.6Hz),
5.92 (1H, d, J = 5.4Hz), 6.12 (1H, br t, J = 8.3Hz), 7.35 (2H, d, J = 6.2Hz),
7.48 (2H, t, J = 7.6Hz), 7.62 (1H, t, J = 7.6Hz), 8.10 (2H, d, J = 7.6Hz),
8.60 (2H, d, J = 6.2Hz)
FAB mass: 853 (MH+)
[0359]
Example 73
7 α, 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-7-deoxy-9- Dihydro-7-fluoro-9,10-O- (2-morpholinoethylidene) baccatin III
[0360]
Melting point: 134-138.5 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.19 (3H, s), 1.41 (9H, s), 1.57 (3H, s), 1.63 (3H, s), 1.72 (3H, s),
1.81 (1H, s), 2.10-2.50 (4H, m), 2.33 (3H, s), 2.50-2.75 (4H, m),
2.82-2.93 (2H, m), 3.49 (1H, d, J = 5.2Hz), 3.75 (4H, t, J = 4.6Hz),
4.00 (1H, br s), 4.21 (1H, br d, J = 8.8Hz), 4.26 (1H, d, J = 8.3Hz),
4.49 (1H, d, J = 8.3Hz), 4.71 (1H, br s), 4.76 (1H, br d, J = 46.5Hz),
4.91 (1H, t, J = 4.2Hz), 4.96 (1H, br d, J = 6.4Hz), 5.33-5.42 (3H, m),
5.91 (1H, d, J = 5.2Hz), 6.10 (1H, br t, J = 8.3Hz), 6.32 (1H, d, J = 2.9Hz),
6.34-6.38 (1H, m), 7.38 (1H, br s), 7.49 (2H, t, J = 7.3Hz),
7.61 (1H, t, J = 7.3Hz), 8.10 (2H, d, J = 7.3Hz)
FAB mass: 913 (MH+)
[0361]
Example 74
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-7-deoxy-9-dihydro-9,10- O- (2-morpholinoethylidene) baccatin III
[0362]
Melting point: 146-149 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDCl3 / TMS) δ (ppm)
1.24 (3H, s), 1.40 (9H, s), 1.46 (3H, s), 1.59 (3H, s), 1.60-2.10 (5H, m),
2.27 (3H, s), 2.30-2.45 (1H, m), 2.58-2.94 (6H, m), 2.90 (1H, d, J = 4.4Hz),
3.74 (4H, t, J = 4.8Hz), 4.09 (1H, d, J = 7.4Hz), 4.23 (1H, d, J = 8.8Hz),
4.31 (1H, d, J = 8.8Hz), 4.50 (1H, br), 4.62 (1H, s), 4.91 (1H, s),
5.04 (1H, t, J = 3.9Hz), 5.22 (1H, d, J = 7.4Hz), 5.31 (1H, d, J = 9.3Hz),
5.70 (1H, d, J = 9.3Hz), 6.05 (1H, d, J = 4.4Hz), 6.05-6.18 (1H, m),
7.20-7.48 (7H, m), 7.60 (1H, t, J = 7.3Hz), 8.11 (2H, d, J = 7.3Hz).
FAB mass ： 905 (MH+)
[0363]
Example 75
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -10-deacetyl-7-deoxy-9,10- O-ethylidene-9-dihydrobaccatin III
[0364]
Melting point: 120-122 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDCl3 / TMS) δ (ppm)
1.10-2.10 (5H, m), 1.23 (3H, s), 1.25 (3H, s), 1.42 (9H, s),
1.49 (3H, d, J = 5.3Hz), 1.57 (3H, s), 1.61 (3H, s), 2.20-2.40 (1H, m),
2.26 (3H, s), 2.90 (1H, d, J = 4.9Hz), 4.08 (1H, d, J = 7.3Hz),
4.25 (1H, d, J = 8.8Hz), 4.32 (1H, d, J = 8.8Hz), 4.62 (1H, s), 4.80-5.00 (2H, m),
5.06 (1H, q, J = 5.3Hz), 5.22 (1H, d, J = 7.3Hz), 5.32 (1H, d like, J = 9.3Hz),
5.79 (1H, d like, J = 9.3Hz), 6.03 (1H, d, J = 4.9Hz), 6.05-6.20 (1H, m),
7.38 (2H, d, J = 4.8Hz), 7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.11 (2H, d, = 7.8Hz), 8.61 (2H, d, J = 4.8Hz).
FAB mass ： 821 (MH+)
[0365]
Example 76
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-ethyl-2-hydroxy-3- (4-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl- 9-Dihydro-9,10-O-isopropylidenebaccatin III
[0366]
Melting point: 125-164 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.95 (3H, t, J = 6.8Hz), 1.11-1.48 (6H, m), 1.25 (6H, s), 1.29 (3H, s),
1.66 (3H, s), 1.90-2.37 (5H, m), 2.89 (1H, d, J = 4.4Hz),
3.71 (1H, d, J = 7.3Hz), 4.06 (1H, m), 4.31 (2H, s),
4.67 (1H, d, J = 8.3Hz), 5.01 (1H, d, J = 9.8Hz), 5.05 (1H, s),
5.45 (1H, d, J = 6.8Hz), 5.91 (1H, d, J = 9.8Hz), 6.07 (1H, d, J = 4.4Hz),
6.21 (1H, t, J = 8.0Hz), 7.36 (2H, d, J = 5.9Hz), 7.49 (2H, t, J = 7.3Hz),
7.62 (1H, t, J = 7.3Hz), 8.04 (2H, d, J = 8.3Hz), 8.56 (2H, d, J = 5.4Hz).
FAB mass ： 905 (MH+).
[0367]
Example 77
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-7-deoxy-9-dihydro- 9,10-O- (2-propenylidene) baccatin III
[0368]
Melting point: 133-136 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.42 (9H, s), 1.49 (3H, s), 1.63 (3H, s), 1.75 (3H, s),
1.80-2.15 (5H, m), 2.30-2.44 (1H, m), 2.33 (3H, s), 2.93 (1H, d, J = 4.9Hz),
4.17 (1H, d, J = 6.8Hz), 4.23 (1H, d, J = 8.8Hz), 4.33 (1H, d, J = 8.8Hz),
4.72 (1H, s), 4.92 (1H, s), 5.24 (1H, d, J = 6.3Hz), 5.30 (1H, d, J = 6.8Hz),
5.38 (1H, d, J = 10.2Hz), 5.42-5.54 (2H, m), 5.58 (1H, d, J = 17.5Hz),
5.96-6.08 (2H, m), 6.11 (1H, t, J = 7.9Hz), 6.31 (1H, d, J = 3.4Hz),
6.34 (1H, dd, J = 3.4Hz, J = 1.9Hz), 7.39 (1H, s like), 7.47 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz).
FAB mass ： 822 (MH+)
[0369]
Example 78
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-ethyl-2-hydroxy-3- (4-pyridyl) propionyl] -10-deacetyl-9-dihydro-9,10-O- Isopropylidenebaccatin III
[0370]
Melting point: 161-163 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.95 (3H, t, J = 7.3Hz), 1.26 (3H, s), 1.30 (3H, s), 1.36 (9H, s),
1.39 (3H, s), 1.57 (3H, s), 1.62 (3H, s), 1.67 (3H, s),
1.82-2.35 (4H, m), 2.49 (3H, s), 2.89 (1H, d, J = 4.4Hz),
3.75 (1H, d, J = 7.3Hz), 4.06 (1H, br), 4.38 (2H, s),
4.67 (1H, d, J = 7.8Hz), 5.01 (1H, d, J = 9.8Hz), 5.10 (1H, s),
5.45 (1H, d, J = 6.8Hz), 5.82 (1H, brd, J = 9.3Hz), 6.04 (1H, d, J = 4.4Hz),
6.24 (1H, t, J = 8.0Hz), 7.36 (2H, d, J = 5.4Hz), 7.48 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.3Hz), 8.24 (2H, d, J = 7.3Hz), 8.56 (2H, d, J = 5.4Hz).
FAB mass ： 879 (MH+).
[0371]
Example 79
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-7-deoxy-9-dihydro- 9,10-O- (2-morpholinoethylidene) baccatin III
[0372]
Melting point: 140-143 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.41 (9H, s), 1.47 (3H, s), 1.60 (3H, s), 1.60-2.15 (5H, m),
1.73 (3H, s), 2.20-2.42 (1H, m), 2.32 (3H, s), 2.52-2.84 (6H, m),
2.92 (1H, d, J = 4.9Hz), 3.74 (4H, t, J = 4.4Hz), 4.11 (1H, d, J = 6.9Hz),
4.23 (1H, d, J = 8.3Hz), 4.32 (1H, d, J = 8.3Hz), 4.72 (1H, s), 4.91 (1H, s),
5.04 (1H, t, J = 3.9Hz), 5.24 (1H, d, J = 6.9Hz), 5.45 (1H, d, J = 9.3Hz),
5.99 (1H, d, J = 4.9Hz), 6.03-6.18 (1H, m), 6.31 (1H, s like),
6.34 (1H, s like), 7.38 (1H, s like), 7.47 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz).
FAB mass ： 895 (MH+)
[0373]
Example 80
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-pyridyl) propionyl] -10-deacetyl-7-deoxy-9-dihydro- 9,10-O-isopropylidenebaccatin III
[0374]
Melting point: 145-148 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.43 (3H, s), 1.44 (9H, s), 1.52 (3H, s), 1.56 (3H, s),
1.61 (3H, s), 1.71 (3H, s), 1.80-2.20 (4H, m), 2.22-2.31 (2H, m),
2.35 (3H, s), 2.94 (1H, d, J = 4.9Hz), 4.17 (1H, d, J = 7.3Hz),
4.23 (1H, d, J = 8.3Hz), 4.32 (1H, d, J = 8.3Hz), 4.88 (1H, d, J = 2.5Hz),
4.92 (1H, s), 5.34 (1H, d, J = 9.3Hz), 5.56 (1H, d, J = 7.3Hz),
5.94 (1H, d, J = 9.3Hz), 5.96 (1H, d, J = 4.9Hz), 6.09 (1H, t, J = 8.3Hz),
7.22 (1H, dd, J = 7.3Hz, J = 4.9Hz), 7.38-7.50 (3H, m), 7.59 (1H, t, J = 7.8Hz),
7.72 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.8Hz), 8.54 (1H, d, J = 4.4Hz).
FAB mass ： 835 (MH+)
[0375]
Example 81
7 α, 9β-4- O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -7-deoxy- 4,10-dideacetyl-9-dihydro-7-fluoro-9,10-O- (2-morpholinoethylidene) baccatin III
[0376]
Melting point: 124.5-129.5 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.02 (3H, t, J = 7.3Hz), 1.19 (3H, s), 1.40 (9H, s), 1.57 (3H, s), 1.63 (3H, s),
1.72 (3H, s), 1.81 (1H, s), 1.75-1.90 (2H.m), 2.15-2.55 (6H, m),
2.55-2.67 (4H, m), 2.82-2.93 (2H, m), 3.49 (1H, d, J = 5.4Hz),
3.74 (4H, t, J = 5.1Hz), 3.92 (1H, br s), 4.22 (1H, d, J = 8.3Hz),
4.27 (1H, d, J = 8.3Hz), 4.39 (1H, d, J = 8.3Hz), 4.66-4.73 (1H, br),
4.68-4.85 (1H, m), 4.87-4.95 (2H, m), 5.30-5.41 (3H, m),
5.91 (1H, d, J = 5.4Hz), 6.08 (1H, br t, J = 8.1Hz), 6.33 (1H, d, J = 3.4Hz),
6.36 (1H, dd, J = 3.4, J = 1.5Hz), 7.39 (1H, d, J = 1.5Hz), 7.48 (2H, t, J = 7.8Hz),
7.62 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz)
[0377]
Example 82
9 β-13-O- [3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3- (2-pyridyl) propionyl] -10-deacetyl-7-deoxy-9-dihydro-9, 10-O-isopropylidenebaccatin III
[0378]
Melting point: 147-150 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.29 (3H, s), 1.40 (3H, s), 1.42 (9H, s), 1.52 (3H, s), 1.54 (3H, s),
1.55 (6H, s), 1.61 (3H, s), 1.80-2.23 (6H, m), 2.51 (3H, s),
2.94 (1H, d, J = 4.9Hz), 4.18 (1H, d, J = 7.3Hz), 4.22 (1H, d, J = 7.3Hz),
4.34 (1H, d, J = 8.3Hz), 4.94 (1H, s), 5.10 (1H, d, J = 10.2Hz),
5.49 (1H, d, J = 7.3Hz), 6.03 (1H, d, J = 10.2Hz), 6.15 (1H, t, J = 8.8Hz),
7.18-7.33 (1H, m), 7.37-7.55 (3H, m), 7.60 (1H, t, J = 7.4Hz),
7.67-7.80 (1H, m), 8.15 (2H, d, J = 7.4Hz), 8.49 (1H, d, J = 4.4Hz).
FAB mass ： 849 (MH+)
[0379]
Example 83
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-pyridyl) propionyl] -4,10-dideacetyl-9-dihydro-9, 10-O-isopropylidene-4-O-propionylbaccatin III
[0380]
Melting point: 148-150 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.28 (3H, s), 1.32 (3H, t, J = 7.5Hz), 1.40 (3H, s), 1.44 (9H, s), 1.58 (3H, s),
1.65 (3H, s), 1.66 (3H, s), 2.18 (2H, br), 2.27 (1H, m), 2.68 (2H, q, J = 7.5Hz),
2.96 (1H, d, J = 4.9Hz), 3.88 (1H, d, J = 7.3Hz), 4.06 (1H, m),
4.32 (1H, d, J = 8.3Hz), 4.41 (1H, d, J = 8.3Hz), 4.68 (1H, d, J = 7.8Hz),
4.85 (1H, br), 5.05 (1H, t-br), 5.32 (1H, m), 5.52 (1H, d, J = 7.3Hz),
5.87 (1H, d, J = 9.9Hz), 6.03 (1H, d, J = 4.9Hz), 6.09 (1H, t, J = 8.8Hz),
7.24 (1H, m), 7.42 (1H, d, J = 7.8Hz), 7.47 (2H, t, J = 7.5Hz),
7.60 (1H, t, J = 7.5Hz), 7.73 (1H, td, J = 7.8Hz, J = 2Hz), 8.13 (2H, m),
8.52 (1H, d, J = 4.4Hz).
FAB mass ： 866 (MH+)
[0381]
Example 84
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (2-pyridyl) propionyl] -10-deacetyl-9-dihydro-9,10-O- Isopropylidenebaccatin III
[0382]
Melting point: 145-151 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.29 (3H, s), 1.38 (3H, s), 1.44 (9H, s), 1.50 (3H, s), 1.55 (3H, s),
1.56 (3H, s), 1.64 (3H, s), 1.66 (3H, s), 2.07-2.30 (4H, m),
2.55 (3H, s), 2.94 (1H, d, J = 5.4Hz), 3.86 (1H, d, J = 7.3Hz), 4.05 (1H, m),
4.36 (2H, AB type q, J = 8.3Hz), 4.69 (1H, d, J = 7.8Hz), 5.10 (1H, d, J = 10.3Hz),
5.11 (1H, s like), 5.45 (1H, d, J = 7.8Hz), 5.99-6.03 (2H, m),
6.16 (1H, t, J = 9.3Hz), 7.24 (1H, m), 7.43-7.48 (3H, m),
7.60 (1H, t, J = 7.3Hz), 7.73 (1H, t, J = 6.8Hz), 8.14 (2H, d, J = 7.8Hz),
8.47 (1H, d, J = 4.4Hz).
FAB mass ： 865 (MH+).
[0383]
Example 85
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (2-pyridyl) propionyl] -4,10-dideacetyl-9-dihydro-9,10- O-isopropylidene-4-O-propionylbaccatin III
[0384]
Melting point: 147-150 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (s), 1.38 (s), 1.40 (3H, t, J = 7.3Hz), 1.44 (9H, s), 1.50 (s), 1.55 (s),
1.57 (s), 1.64 (s), 1.65 (s), 2.12 (1H, dd, J = 14.7Hz, J = 8.8Hz),
2.20 (2H, t, J = 3.4Hz), 2.29 (1H, dd, J = 14.7Hz, J = 8.8Hz), 2.88 (2H, q, J = 7.5Hz),
2.94 (1H, d, J = 5.4Hz), 3.88 (1H, d, J = 7.3Hz), 4.05 (1H, m),
4.32 (1H, d, J = 8.3Hz), 4.44 (1H, d, J = 8.3Hz), 4.67 (1H, d, J = 7.8Hz),
5.07 (1H, m), 5.45 (1H, d, J = 7.3Hz), 6.01 (2H, m), 6.14 (1H, t, J = 9Hz),
7.24 (1H, m), 7.44 (1H, d, J = 8.3Hz), 7.48 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.3Hz), 7.73 (1H, td, J = 7.5Hz, J = 1.5Hz), 8.14 (2H, m),
8.47 (1H, d, J = 4.4Hz).
FAB mass ： 879 (M+).
[0385]
Example 86
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-pyridyl) propionyl] -10-deacetyl-9-dihydro-9,10- O-isopropylidenebaccatin III
[0386]
Melting point: 150-153 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.40 (3H, s), 1.44 (9H, s), 1.58 (3H, s), 1.64 (3H, s),
1.66 (3H, s), 1.69 (3H, s), 2.05-2.32 (4H, m), 2.40 (3H, s),
2.95 (1H, d, J = 4.9Hz), 3.86 (1H, d, J = 7.8Hz), 4.06 (1H, m),
4.35 (2H, AB type q, J = 8.3Hz), 4.70 (d, J = 8.3Hz), 4.85 (1H, d, J = 2.4Hz),
5.11 (1H, s), 5.35 (1H.d, J = 9.3Hz), 5.53 (1H, d, J = 7.3Hz),
5.90 (1H, d, J = 9.8Hz), 6.03 (1H, d, J = 5.4Hz), 6.10 (1H, t, J = 8.3Hz),
7.24 (1H, m), 7.41 (1H, d, J = 7.8Hz), 7.47 (2H, t, J = 7.8Hz),
7.59 (1H, t, J = 7.3Hz), 7.73 (1H, t, J = 5.9Hz), 8.11 (2H, d, J = 8.8Hz),
8.52 (1H, d, J = 4.9Hz).
FAB mass ： 852 (MH2 +).
[0387]
Example 87
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (2-pyridyl) propionyl] -10-deacetyl-9-dihydro-9,10-O- (2-propenylidene) baccatin III
[0388]
Melting point: 140-145 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (3H, s), 1.44 (9H, s), 1.52 (3H, s), 1.54 (3H, s), 1.62 (3H, s),
1.68 (3H, s), 2.13-2.30 (4H, m), 2.55 (3H, s), 2.95 (1H, d, J = 4.9Hz),
3.89 (1H, d, J = 6.8Hz), 4.08 (1H, m), 4.35 (2H, AB type q, J = 8.3Hz),
4.61 (1H, d, J = 8.3Hz), 5.12 (3H, m), 5.19 (1H, d, J = 6.4Hz),
5.45 (1H, d, J = 10.7Hz), 5.56 (1H, d, J = 17.6Hz), 6.01 (2H, m),
6.17 (2H, m), 7.24 (1H, m), 7.43-7.51 (3H, m), 7.61 (1H, t, J = 7.3Hz),
7.73 (1H, t, J = 6.4Hz), 8.13 (2H, d, J = 7.3Hz), 8.48 (1H, d, J = 4.4Hz).
FAB mass ： 864 (MH2 +).
[0389]
Example 88
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (2-pyridyl) propionyl] -10-deacetyl-9-dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0390]
Melting point: 135-139 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (3H, s), 1.43 (9H, s), 1.51 (3H, s), 1.54 (3H, s), 1.61 (3H, s),
1.64 (3H, s), 2.09-2.34 (4H, m), 2.55 (3H, s), 2.62 (4H, m),
2.77 (2H, AB type dq, J = 26.9Hz, J = 3.4Hz), 2.95 (1H, d, J = 4.9Hz),
3.73 (4H, t like, 4.9Hz), 3.81 (1H, d, J = 7.3Hz), 4.07 (1H, m),
4.35 (2H, AB type q, J = 8.3Hz), 4.71 (1H, d, J = 8.3Hz), 4.99 (1H, t, J = 4.4Hz),
5.10 (1H, d, J = 10.3Hz), 5.12 (1H, d, J = 7.3Hz), 6.01 (1H, d, J = 5.4Hz),
6.02 (1H, d, J = 4.9Hz), 6.16 (1H, t, J = 7.8Hz), 7.23 (1H, m),
7.43 (1H, d, J = 7.8Hz), 7.49 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.8Hz),
7.73 (1H, t, J = 7.8Hz), 8.13 (2H, d, J = 7.3Hz), 8.47 (1H, d, J = 4.9Hz).
FAB mass ： 936 (MH+).
[0390]
Example 89
9 β-13-O-[(2R, 3S) -3- (Benzoylamino) -2-hydroxy-3-phenylpropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl-7-deoxy-9 -Dihydro-9,10-O- (2-propenylidene) baccatin III
[0392]
Melting point: 150-153 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.05-1.13 (2H, m), 1.21 (3H, s), 1.38-1.50 (2H, m), 1.43 (3H, s),
1.46 (3H, s), 1.55-1.75 (2H, m), 1.60 (3H, s), 1.78-2.11 (5H, m),
2.38 (1H, dd, J = 15.1Hz, J = 9.7Hz), 2.85 (1H, d, J = 4.9Hz),
4.09 (1H, d, J = 6.9Hz), 4.18 (1H, d, J = 8.8Hz), 4.27 (1H, d, J = 8.8Hz),
4.73 (1H, s like), 4.88 (1H, s like), 4.93 (1H, s like), 5.18-5.27 (2H, m),
5.44 (1H, d, J = 10.3Hz), 5.55 (1H, d, J = 17.1Hz),
5.85 (1H, dd, J = 9.3Hz, J = 2.5Hz), 5.94-6.09 (3H, m), 7.24-7.57 (11H, m),
7.60 (1H, t, J = 7.3Hz), 7.84 (2H, d like, J = 8.3Hz), 8.04 (2H, d, J = 7.3Hz).
FAB mass ： 862 (MH+)
[0393]
Example 90
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -4,10-dideacetyl-9-dihydro-9,10- O-isopropylidene-4-O-propionylbaccatin III
[0394]
Melting point: 152-155 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.30 (s), 1.38 (s), 1.40 (s), 1.41 (s), 1.44 (s), 1.58 (s), 1.68 (s),
2.06 (1H, m), 2.10 (1H, m), 2.22 (1H, m), 2.26 (1H, m), 2.63 (1H, m),
2.75 (1H, m), 2.91 (1H, d, J = 4.4Hz), 3.78 (1H, d, J = 7.8Hz), 4.08 (1H, br),
4.39 (2H, AB type q, J = 8.8Hz), 4.70 (1H, d, J = 7.8Hz), 4.99 (1H, d, J = 9.8Hz),
5.48 (1H, d, J = 7.3Hz), 5.78 (1H, d, J = 9.8Hz), 6.06 (1H, d, J = 4.3Hz),
6.21 (1H, t-br), 7.35 (2H, d, J = 5Hz), 7.48 (2H, t, J = 7.8Hz),
7.61 (1H, t, J = 7.3Hz), 8.14 (2H, m), 8.59 (2H, d, J = 5Hz).
FAB mass ： 879 (M+).
[0395]
Example 91
9 β-13-O-[(2R, 3S) -3- (Benzoylamino) -2-hydroxy-3-phenylpropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl-7-deoxy-9 -Dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0396]
Melting point: 150-153 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.04-1.13 (2H, m), 1.21 (3H, s), 1.36-1.47 (2H, m), 1.42 (3H, s),
1.44 (3H, s), 1.53-2.08 (7H, m), 1.57 (3H, s),
2.37 (1H, dd, J = 15.1Hz, J = 9.8Hz), 2.53-2.73 (5H, m),
2.77 (1H, dd, J = 13.6Hz, J = 3.9Hz), 2.85 (1H, d, J = 4.4Hz),
3.73 (4H, t, J = 4.4Hz), 4.17 (1H, d, J = 6.8Hz), 4.26 (1H, d, J = 8.8Hz),
4.30 (1H, d, J = 8.8Hz), 4.73 (1H, d, J = 2.4Hz), 4.87 (1H, br s),
5.00 (1H, t, J = 4.4Hz), 5.14 (1H, d, J = 6.8Hz), 5.85 (1H, dd, J = 9.3Hz, J = 2.5Hz),
5.97-6.06 (2H, m), 7.23-7.56 (10H, m), 7.60 (1H, t, J = 7.3Hz),
7.84 (1H, d, J = 7.3Hz), 8.04 (2H, d, J = 7.3Hz).
FAB mass ： 935 (MH+)
[0397]
Example 92
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4-O-ethoxycarbonyl-4,10-dideacetyl-9-dihydro -9,10-O- (2-propenylidene) baccatin III
[0398]
Melting point: 117-120 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.34 (3H, t, J = 7.4Hz), 1.40 (9H, s), 1.62 (3H, s),
1.65 (3H, br s), 1.67 (3H, s), 1.88 (1H, s), 1.99-2.29 (3H, m),
2.47 (1H, dd, J = 15.1Hz, J = 9.7Hz), 2.86 (1H, d, J = 4.3Hz),
3.87 (1H, d, J = 6.8Hz), 3.97 (1H, br), 4.08 (1H, m), 4.30-4.66 (6H, m),
5.17-5.36 (3H, m), 5.45 (1H, d, J = 10.8Hz), 5.57 (1H, d, J = 17.1Hz),
5.66 (1H, d, J = 9.7Hz), 5.92 (1H, br t, J = 7.3Hz),
6.03 (1H, ddd, J = 17.1Hz, J = 10.8Hz, J = 6.3Hz), 6.11 (1H, d, J = 4.3Hz),
7.24-7.49 (7H, m), 7.58 (1H, t, J = 7.3Hz), 8.03 (2H, d, J = 7.3Hz).
FAB mass ： 878 (MH+).
[0399]
Example 93
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-ethoxycarbonyl-4,10-dideacetyl -9-Dihydro-9,10-O- (2-propenylidene) baccatin III
[0400]
Melting point: 121-123 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.37 (3H, t, J = 6.9Hz), 1.38 (9H, s), 1.63 (3H, s), 1.68 (3H, s),
1.75 (3H, s), 1.88 (1H, s), 2.02-2.12 (1H, m), 2.18-2.37 (2H, m),
2.45 (1H, dd, J = 15.2Hz, J = 9.8Hz), 2.88 (1H, d, J = 4.9Hz), 3.80-3.94 (2H, m),
4.08 (1H, br), 4.29-4.61 (5H, m), 4.70 (1H, s like), 5.18-5.29 (2H, m),
5.29 (1H, d, J = 7.0Hz), 5.30-5.45 (2H, m), 5.46 (1H, d, J = 10.7Hz),
5.57 (1H, d, J = 17.0Hz), 5.97-6.15 (2H, m), 6.10 (1H, d, J = 4.9Hz),
7.38 (1H, s like), 7.44 (2H, t, J = 7.8Hz), 7.58 (1H, t, J = 7.8Hz),
8.05 (2H, d, J = 7.8Hz).
FAB mass ： 868 (MH+).
[0401]
Example 94
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4-O-ethoxycarbonyl-4,10-dideacetyl-9-dihydro -9,10-O- (2-morpholinoethylidene) baccatin III
[0402]
Melting point: 128-131 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.33 (3H, t, J = 7.3Hz), 1.40 (9H, s), 1.60 (3H, s), 1.64 (6H, s),
1.86 (1H, s), 2.00-2.09 (1H, m), 2.14-2.30 (2H, m),
2.46 (1H, dd, J = 15.1Hz, J = 9.7Hz), 2.56-2.71 (4H, m),
2.75 (1H, dd, J = 13.6Hz, J = 5.3Hz), 2.80-2.91 (2H, m), 3.73 (4H, t, J = 5.3Hz),
3.78 (1H, d, J = 7.3Hz), 4.06 (1H, br), 4.29-4.48 (3H, m), 4.50-4.68 (3H, m),
5.03 (1H, t like, J-5.3Hz), 5.19-5.35 (3H, m), 5.65 (1H, d, J = 9.8Hz),
5.92 (1H, br t, J = 6.8Hz), 6.09 (1H, d, J = 4.4Hz), 7.25-7.50 (7H, m),
7.59 (1H, t, J = 7.8Hz), 8.03 (2H, d, J = 7.8Hz).
FAB mass ： 951 (MH+).
[0403]
Example 95
9 β-13-O- [3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -10-deacetyl-7-deoxy-9-dihydro-9, 10-O-isopropylidenebaccatin III
[0404]
Melting point: 182-184 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.37 (9H, s), 1.42 (6H, s), 1.47 (3H, br s), 1.50 (3H, s),
1.56 (3H, s), 1.62 (3H, s), 1.75-2.11 (6H, m),
2.22 (1H, dd, J = 14.2Hz, J = 10.2Hz), 2.30-2.50 (1H, m), 2.42 (3H, s),
2.91 (1H, d, J = 4.4Hz), 4.12 (1H, d, J = 7.3Hz), 4.28 (1H, d, J = 8.3Hz),
4.32 (1H, d, J = 8.3Hz), 4.58 (1H, br), 4.92 (1H, s), 5.00 (1H, d, J = 10.2Hz),
5.51 (1H, d, J = 7.3Hz), 5.92 (1H, d, J = 10.2Hz), 5.98 (1H, d, J = 4.4Hz),
6.17-6.29 (1H, m), 7.36 (2H, d, J = 5.4Hz), 7.47 (2H, t, J = 7.9Hz),
7.60 (1H, t, J = 7.9Hz), 8.13 (2H, d, J = 7.9Hz), 8.58 (2H, d, J = 5.4Hz).
FAB mass ： 849 (MH+).
[0405]
Example 96
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-ethoxycarbonyl-4,10-dideacetyl -9-Dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0406]
Melting point: 130-132 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.26 (3H, s), 1.36 (3H, t, J = 6.8Hz), 1.41 (9H, s), 1.61 (3H, s), 1.65 (3H, s),
1.73 (3H, s), 1.85 (1H, s), 2.00-2.10 (1H, m), 2.19-2.39 (2H, m),
2.42 (1H, dd, J = 15.1Hz, J = 9.8Hz), 2.54-2.93 (7H, m), 3.73 (4H, t, J = 4.4Hz),
3.80 (1H, d, J = 7.3Hz), 4.06 (1H, br), 4.25-4.50 (3H, m),
4.53 (1H, d, J = 8.8Hz), 4.61 (1H, d, J = 7.8Hz), 4.70 (1H, s),
5.03 (1H, t, J = 4.4Hz), 5.17-5.45 (4H, m), 5.99 (1H, t, J = 7.8Hz),
6.08 (1H, d, J = 4.4Hz), 6.28-6.42 (2H, m), 7.38 (1H.s like),
7.45 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.05 (2H, d, J = 7.8Hz).
FAB mass ： 941 (MH+).
[0407]
Example 97
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-thienyl) propionyl] -10-deacetyl-7-deoxy-9-dihydro- 9,10-O- (2-propenylidene) baccatin III
[0408]
Melting point: 135-137 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.41 (9H, s), 1.48 (3H, s), 1.63 (3H, s), 1.66 (3H, s),
1.80-2.22 (5H, m), 2.31 (3H, s), 2.37 (1H, dd, J = 15.1Hz, J = 10.2Hz),
2.92 (1H, d, J = 5.3Hz), 4.16 (1H, d, J = 6.9Hz), 4.24 (1H, d, J = 8.8Hz),
4.33 (1H, d, J = 8.8Hz), 4.57 (1H, s), 4.64 (1H, s), 4.93 (1H, s),
5.23 (1H, d, J = 6.4Hz), 5.29 (1H, d, J = 6.9Hz), 5.46 (1H, d, J = 10.8Hz),
5.50-5.74 (3H, m), 5.96-6.18 (3H, m), 6.98 (1H, dd, J = 5.4Hz, J = 4.0Hz),
7.10 (1H, d, J = 4.0Hz), 7.22-7.27 (1H, m), 7.47 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz).
FAB mass ： 838 (MH+).
[0409]
Example 98
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-thienyl) propionyl] -10-deacetyl-7-deoxy-9-dihydro- 9,10-O- (2-morpholinoethylidene) baccatin III
[0410]
Melting point: 135-138 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.41 (9H, s), 1.47 (3H, s), 1.59 (3H, s), 1.60-2.15 (5H, m),
1.65 (3H, s), 2.31 (3H, s), 2.36 (1H, dd, J = 15.2Hz, J = 9.8Hz),
2.57-2.86 (6H, m), 2.91 (1H, d, J = 4.9Hz), 3.74 (4H, t, J = 4.8Hz),
4.10 (1H, d, J = 6.8Hz), 4.23 (1H, d, J = 8.3Hz), 4.32 (1H, d, J = 8.3Hz),
4.64 (1H, s), 4.92 (1H, s), 5.04 (1H, t, J = 3.9Hz), 5.22 (1H, d, J = 6.8Hz),
5.54 (1H, d, J = 9.8Hz), 5.60 (1H, d, J = 9.8Hz), 5.99 (1H, d, J = 4.9Hz),
6.08 (1H, t, J = 7.8Hz), 6.97 (1H, dd, J = 5.3Hz, J = 3.4Hz), 7.10 (1H, d, J = 3.4Hz),
7.20-7.20 (1H, m), 7.47 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.8Hz),
8.12 (2H, d, J = 7.8Hz).
FAB mass ： 911 (MH+).
[0411]
Example 99
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-pyridyl) propionyl] -4,10-dideacetyl-9-dihydro-4- O-Ethoxycarbonyl-9,10-O-isopropylidenebaccatin III
[0412]
Melting point: 131-135 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.37 (3H, t, J = 7.3Hz), 1.41 (3H, s), 1.45 (9H, s),
1.59 (3H, s), 1.65 (6H, s), 1.74 (3H, s), 1.87-2.39 (1H, d, J = 4.4Hz),
2.86 (1H, d, J = 4.4Hz), 3.63 (1H, d, J = 7.3Hz), 4.04 (1H, m),
4.34 (2H, m), 4.48 (1H, q, J = 7.3Hz), 4.53 (1H, d, J = 8.8Hz),
4.67 (1H, d, J = 7.8Hz), 4.80 (1H, d, J = 2.8Hz), 5.23 (1H, d, J = 7.8Hz),
5.57 (1H, d, J = 7.3Hz), 5.59 (2H, m), 6.07 (1H, d, J = 4.9Hz),
7.24 (1H, dd, J = 7.3Hz, J = 4.9Hz), 7.45 (2H, t, J = 7.8Hz),
7.58 (1H, t, J = 7.3Hz), 7.73 (1H, dt, J = 7.8Hz, J = 2.0Hz),
8.05 (2H, d, J = 7.2Hz), 8.50 (1H, d, J = 3.9Hz).
FAB mass ： 881 (MH+).
[0413]
Example 100
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -4,10-dideacetyl-9-dihydro-4- O-Ethoxycarbonyl-9,10-O-isopropylidenebaccatin III
[0414]
Melting point: 132-137 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23 (3H, s), 1.37 (3H, t, J = 7.3Hz), 1.41 (9H, s), 1.59 (3H, s),
1.62 (3H, s), 1.64 (3H, s), 1.66 (6H, s), 2.02-2.48 (4H, m),
2.87 (1H, d, J = 4.4Hz), 3.79 (1H, d, J = 7.3Hz), 4.06 (1H, m),
4.35 (1H, d, J = 8.8Hz), 4.43 (2H, q, J = 7.3Hz), 4.52 (1H, d, J = 8.8Hz),
4.62 (2H, s), 5.21 (1H, s), 5.30 (1H, d, J = 8.3Hz),
5.66 (1H, d, J = 7.3Hz), 5.75 (1H, d, J = 9.8Hz), 5.94 (1H, t, J = 8.0Hz),
6.12 (1H, d, J = 4.4Hz), 7.37 (2H, d, J = 4.9Hz), 7.44 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.03 (2H, d, J = 7.3Hz), 8.60 (2H, d, J = 5.4Hz).
FAB mass ： 881 (MH+).
[0415]
Example 101
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -4,10-dideacetyl-9-dihydro-4-O- Ethoxycarbonyl-9,10-O-isopropylidenebaccatin III
[0416]
Melting point: 149-153 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.28 (3H, s), 1.38 (9H, s), 1.41 (3H, s), 1.42 (3H, s),
1.45 (3H, t, J = 7.3Hz), 1.53 (3H, s), 1.59 (3H, s), 1.65 (3H, s),
1.67 (3H, s), 2.02-2.27 (4H, m), 2.91 (1H, d, J = 3.9Hz),
3.78 (1H, d, J = 7.3Hz), 4.06 (1H, m), 4.53 (1H, d, J = 8.8Hz),
4.54 (3H, m), 4.63 (1H, d, 7.8Hz), 5.09 (1H, d, J = 10.3Hz), 5.21 (1H, s),
5.53 (1H, d, J = 7.3Hz), 5.82 (1H, d, J = 9.8Hz), 6.10 (1H, d, J = 4.4Hz),
6.17 (1H, t, J = 8.3Hz), 7.39 (2H, d, J = 4.9Hz), 7.44 (2H, t, J = 7.8Hz),
7.59 (1H, t, J = 7.3Hz), 8.05 (2H, d, J = 7.3Hz), 8.58 (2H, d, J = 4.9Hz).
FAB mass ： 895 (MH+).
[0417]
Example 102
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-7-deoxy-9-dihydro-9,10- O-thiocarbonate baccatin III
[0418]
Melting point: 162-165 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.30 (3H, s), 1.40 (9H, s), 1.50-2.15 (5H, m), 1.61 (3H, s),
1.62 (3H, s), 2.29 (3H, s), 2.41 (1H, dd, J = 15.2Hz, J = 9.8Hz),
2.87 (1H, d, J = 4.9Hz), 4.10 (1H, br), 4.20 (1H, d, J = 8.8Hz),
4.32 (1H, d, J = 8.8Hz), 4.63 (1H, br), 4.85 (1H, d, J = 8.7Hz), 4.90 (1H, s),
5.28 (1H, d, J = 9.2Hz), 5.58 (1H, d, J = 9.2Hz), 5.99 (1H, d, J = 4.9Hz),
6.04-6.18 (2H, m), 7.20-7.45 (5H, m), 7.48 (2H, t, J = 7.8Hz),
7.62 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
FAB mass ： 836 (MH+).
[0419]
Example 103
7 α, 9β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy- (2-pyridyl) propionyl] -10-deacetyl-7-deoxy-9-dihydro- 7-Fluoro-9,10-O-isopropylidenebaccatin III
[0420]
Melting point: 136-141 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.21 (3H, s), 1.42 (3H, s), 1.44 (9H, s), 1.52 (3H, s), 1.59 (3H, s),
1.65 (3H, s), 1.70 (1H, s), 1.74 (3H, s), 2.07-2.45 (4H, m),
2.27 (1H, d, J = 9.3Hz), 2.41 (3H, s), 3.50 (1H, d, J = 5.4Hz),
4.29 (1H, d, J = 8.8Hz), 4.36 (1H, d, J = 8.8Hz), 4.62 (1H, d, J = 9.1Hz),
4.84 (1H, br s), 4.83-5.02 (1H, m), 4.95-5.02 (1H, m),
5.36 (1H, br d, J = 9.8Hz), 5.53 (1H, d, J = 9.1Hz), 5.86-5.95 (2H, m),
6.10 (1H, br t, J = 8.5Hz), 7.23 (1H, dd, J = 4.9, J = 7.1Hz), 7.41 (1H, d, J = 7.8Hz),
7.48 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz), 7.73 (1H, dt, J = 1.5, J = 7.8Hz),
8.21 (2H, d, J = 7.63Hz), 8.46 (1H, d, J = 4.9Hz)
FAB mass: 853 (MH+)
[0421]
Example 104
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-7-deoxy-9-dihydro- 9,10-O- [2- (1-Methylpiperazin-4-yl) ethylidene] baccatin III
[0422]
Melting point: 128-130 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.42 (9H, s), 1.47 (3H, s), 1.58-2.10 (6H, m), 1.60 (3H, s),
1.73 (3H, s), 2.20-2.88 (9H, m), 2.32 (6H, s), 2.91 (1H, d, J = 4.9Hz),
4.11 (1H, d, J = 6.9Hz), 4.23 (1H, d, J = 8.3Hz), 4.32 (1H, d, J = 8.3Hz),
4.77 (1H, s like), 4.91 (1H, s like), 5.03 (1H, t, J = 3.9Hz),
5.23 (1H, d, J = 6.9Hz), 5.37 (1H, d, J = 9.3Hz), 5.43 (1H, d, J = 9.3Hz),
5.99 (1H, d, J = 4.9Hz), 6.10 (1H, t, J = 8.0Hz), 6.31 (1H, d, J = 3.4Hz),
6.35 (1H, dd, J = 3.4Hz, J = 1.9Hz), 7.39 (1H, d, J = 1.9Hz), 7.47 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz).
FAB mass ： 908 (MH+).
[0423]
Example 105
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-7-deoxy-9-dihydro- 9,10-O- (2-dimethylaminoethylidene) baccatin III
[0424]
Melting point: 135-136 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.42 (9H, s), 1.47 (3H, s), 1.61 (3H, s), 1.70-2.10 (5H, m),
1.74 (3H, s), 2.20-2.35 (1H, m), 2.32 (3H, s), 2.39 (6H, s),
2.67 (1H, dd, J = 13.2Hz, J = 4.9Hz), 2.77 (1H, dd, J = 13.2Hz, J = 4.9Hz),
2.92 (1H, d, J = 4.8Hz), 4.12 (1H, d, J = 7.4Hz), 4.23 (1H, d, J = 8.3Hz),
4.32 (1H, d, J = 8.3Hz), 4.72 (1H, s), 4.92 (1H, s), 5.03 (1H, t like, J = 4.9Hz),
5.25 (1H, d, J = 7.4Hz), 5.37 (1H, d, J = 10.3Hz), 5.45 (1H, d, J = 10.3Hz),
6.00 (1H, d, J = 4.8Hz), 6.10 (1H, t, J = 8.3Hz), 6.31 (1H, d, J = 3.4Hz),
6.35 (1H, dd, J = 3.4Hz, J = 2.1Hz), 7.39 (1H, d, J = 2.1Hz), 7.47 (2H, t, J = 7.4Hz),
7.60 (1H, t, J = 7.4Hz), 8.12 (2H, d, J = 7.4Hz).
FAB mass ： 853 (MH+).
[0425]
Example 106
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (2-pyridyl) propionyl] -4,10-dideacetyl-9-dihydro-4-O- Ethoxycarbonyl-9,10-O-isopropylidenebaccatin III
[0426]
Melting point: 118-122 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.40 (3H, s), 1.42 (3H, t, J = 7.3Hz), 1.45 (9H, s),
1.56 (3H, s), 1.58 (3H, s), 1.64 (3H, s), 1.67 (3H, s),
2.02-2.48 (4H, m), 2.83 (1H, d, J = 4.9Hz), 3.86 (1H, d, J = 7.8Hz),
4.09 (1H, br), 4.12 (1H, d, J = 7.3Hz), 4.51 (3H, m),
4.64 (1H, d, J = 7.3Hz), 5.13 (1H, d, J = 10.3Hz), 5.23 (1H, br),
5.51 (1H, d, J = 9.9Hz), 6.05 (2H, m), 7.23 (1H, m), 7.45 (3H, m),
7.58 (1H, t, J = 7.3Hz), 7.82 (1H, t, J = 6.8Hz), 8.06 (2H, d, J = 7.3Hz),
8.46 (1H, m).
FAB mass ： 895 (MH+).
[0427]
Example 107
9 β-4-O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl-9 -Dihydro-9,10-O- [2- (1-methylpiperazin-4-yl) ethylidene] baccatin III
[0428]
Melting point: 118-128 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.02 (3H, t, J = 7.3Hz), 1.28 (3H, s), 1.41 (9H, s), 1.61 (3H, s),
1.65 (3H, s), 1.70 (3H, s), 1.84 (2H, m), 2.03-3.07 (20H, m),
3.82 (1H, d, J = 7.3Hz), 4.08 (1H, br), 4.36 (2H, AB type q, J = 8.3Hz),
4.70 (1H, s), 5.01 (1H, t, J = 2.8Hz), 5.06 (1H, s),
5.20 (1H, d, J = 7.3Hz), 5.33 (2H, br), 6.03 (1H, d, J = 4.4Hz),
6.09 (1H, t, J = 8.2Hz), 6.33 (1H, d, J = 2.8Hz), 6.36 (1H, d, J = 2.4Hz),
7.39 (1H, s), 7.48 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 6.8Hz),
8.12 (2H, d, J = 7.4Hz).
FAB mass ： 952 (MH+).
[0429]
Example 108
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-thienyl) propionyl] -4-O-ethoxycarbonyl-4,10-dideacetyl -9-Dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0430]
Melting point: 126-130 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.30-1.45 (3H, m), 1.41 (3H, s), 1.61 (3H, s), 1.64 (3H, s),
1.67 (3H, s), 1.84 (1H, s), 2.00-2.12 (1H, m), 2.17-2.30 (2H, m),
2.45 (1H, dd, J = 15.1Hz, J = 9.8Hz), 2.52-2.94 (7H, m),
3.73 (4H, t like, J-4.4Hz), 3.79 (1H, d, J = 7.3Hz), 4.06 (1H, br),
4.13-4.46 (3H, m), 4.46-4.70 (3H, m), 5.03 (1H, t, J = 3.9Hz),
5.16-5.27 (2H, m), 5.53 (2H, br), 5.86-6.02 (1H, m), 6.10 (1H, d, J = 4.4Hz),
6.97 (1H, dd, J = 4.9Hz, J = 3.4Hz), 7.11 (1H, d, J = 3.4Hz), 7.18-7.35 (1H, m),
7.44 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.04 (2H, d, J = 7.8Hz).
FAB mass ： 957 (MH+).
[0431]
Example 109
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-thienyl) propionyl] -4-O-ethoxycarbonyl-4,10-dideacetyl -9-Dihydro-9,10-O- [2- (1-Methylpiperazin-4-yl) ethylidene] Baccatin III
[0432]
Melting point: 132-135 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.20-1.50 (3H, s), 1.24 (3H, s), 1.40 (9H, s), 1.60 (3H, s), 1.64 (3H, s),
1.67 (3H, s), 1.84 (1H, s), 2.00-2.10 (1H, m), 2.10-2.95 (11H, m),
2.31 (3H, s), 3.79 (1H, d, J = 7.3Hz), 4.06 (1H, s), 4.11-4.50 (3H, m),
4.53 (1H, d, J = 8.8Hz), 4.63 (1H, s), 5.01 (1H, t, J = 4.4Hz), 5.21 (2H, s like),
5.52 (2H, br), 5.84-6.02 (1H, m), 6.09 (1H, d, J = 4.9Hz),
6.97 (1H, dd, J = 14.9Hz, J = 3.9Hz), 7.10 (1H, d, J = 3.9Hz), 7.20-7.35 (1H, m),
7.44 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.04 (2H, d, J = 7.8Hz).
FAB mass ： 970 (MH+).
[0433]
Example 110
9 β-13-O-[(2R, 3R) -3- (Benzoylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl-9 -Dihydro-9,10-O- (2-propenylidene) baccatin III
[0434]
Melting point: 151-153 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.04-1.30 (2H, m), 1.25 (3H, s), 1.30-1.55 (2H, m), 1.59 (3H, s),
1.64 (3H, s), 1.67 (3H, s), 1.70-1.86 (1H, m), 1.97 (1H, s),
2.03-2.32 (3H, m), 2.41 (1H, dd, J = 15.1Hz, J = 9.7Hz), 2.90 (1H, d, J = 4.8Hz),
3.85 (1H, d, J = 7.3Hz), 4.07 (1H, br s), 4.27 (1H, d, J = 8.8Hz),
4.32 (1H, d, J = 8.8Hz), 4.42 (1H, br), 4.57 (1H, br d, J = 7.3Hz),
4.79 (1H, d, J = 2.9Hz), 5.06 (1H, s), 5.19 (1H, d, J = 6.3Hz),
5.23 (1H, d, J = 7.3Hz), 5.44 (1H, d, J = 10.7Hz), 5.55 (1H, d, J = 17.6Hz),
5.89-6.18 (4H, m), 6.36 (1H, dd, J = 3.4Hz, J = 2.0Hz), 6.39 (1H, d, J = 3.4Hz).
FAB mass ： 868 (MH+).
[0435]
Example 111
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-9-dihydro-9,10-O- [2- (1-methylpiperazin-4-yl) ethylidene] baccatin III
[0436]
Melting point: 124-127 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree-CDThreeOD (4: 1 (v / v)) / TMS) δ (ppm):
1.10 (4H, m), 1.28 (3H, s), 1.41 (9H, s), 1.57 (3H, s), 1.63 (3H, s),
1.74 (3H, s), 2.04-3.20 (16H, m), 2.70 (3H, s), 3.84 (1H, d, J = 7.8Hz),
4.04 (1H, br), 4.39 (2H, AB type q, J = 7.8Hz), 4.72 (1H, br),
5.00 (1H, t, J = 3.6Hz), 5.05 (1H, s), 5.23 (1H, d, J = 6.8Hz),
5.38 (1H, d, J = 6.8Hz), 6.03 (2H, m), 6.33 (1H, d, J = 2.8Hz),
6.35 (1H, t, J = 2.0Hz), 7.37 (1H, s), 7.48 (2H, t, J = 7.8Hz),
7.61 (1H, t, J = 7.3Hz), 8.05 (2H, d, J = 7.3Hz).
FAB mass ： 951 (MH2 +).
[0437]
Example 112
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-4,10- Dideacetyl-9-dihydro-9,10-O- (2-dimethylaminoethylidene) baccatin III
[0438]
Melting point: 129-136 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm):
1.10 (4H, m), 1.28 (3H, s), 1.42 (9H, s), 1.58 (3H, s), 1.63 (3H, s),
1.75 (3H, s), 2.03-2.36 (5H, m), 2.71 (3H, s), 2.91 (3H, s),
3.12 (2H, m), 3.90 (1H, d, J = 6.8Hz), 4.05 (1H, m),
4.30 (2H, AB type q, J = 8.8Hz), 4.72 (1H, s), 5.06 (1H, s), 5.21 (1H, br),
5.30 (1H, d, J = 6.8Hz), 5.38 (2H, m), 6.03 (2H, m),
6.33 (1H, d, J = 2.8Hz), 6.35 (1H, d, J = 2.0Hz), 7.37 (1H, s),
7.49 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz), 8.04 (2H, d, J = 7.8Hz).
FAB mass ： 896 (MH2 +).
[0439]
Example 113
9 β-13-O-[(2R, 3R) -3- (Benzoylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-4,10-dideacetyl-9 -Dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0440]
Melting point: 148-151 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.04-1.30 (2H, m), 1.25 (3H, s), 1.34-1.53 (2H, m), 1.58 (3H, s),
1.62 (3H, s), 1.63 (3H, s), 1.72-1.84 (1H, m), 1.93 (1H, s),
2.00-2.24 (3H, m), 2.40 (1H, dd, J = 15.1Hz, J = 9.8Hz), 2.52-2.70 (4H, m),
2.73 (1H, dd, J = 13.2Hz, J = 4.9Hz), 2.81 (1H, dd, J = 13.2Hz, J = 3.9Hz),
3.66-3.83 (4H, m), 3.77 (1H, d, J = 6.8Hz), 4.05-4.08 (1H, m),
4.27 (1H, d, J = 8.8Hz), 4.33 (1H, d, J = 8.8Hz9, 4.66 (1H, d, J = 8.3Hz),
4.79 (1H, s like), 5.00 (1H, t, J = 3.9Hz), 5.06 (1H, s), 5.17 (1H, d, J = 6.8Hz),
5.93 (1H, dd, J = 9.3Hz, J = 2.5Hz), 6.02-6.15 (2H, m), 6.35 (1H, d, J = 1.9Hz),
6.36 (1H, dd, J = 3.4Hz, J = 1.9Hz), 7.12 (1H, d, J = 9.3Hz), 7.37 (1H, s like),
7.40-7.59 (5H, m), 7.61 (1H, t, J = 7.8Hz), 7.80 (2H, d, J = 8.3Hz),
8.04 (2H, d, J = 8.3Hz).
FAB mass ： 941 (MH+).
[0441]
Example 114
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl-7-deoxy-4- O-Ethoxycarbonyl-9-dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0442]
Melting point: 118-119 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.37 (3H, t, J = 5.8Hz), 1.41 (9H, s), 1.49 (3H, s),
1.50-2.10 (4H, m), 1.60 (3H, s), 1.77 (3H, s), 1.85 (1H, s),
2.20 (1H, dd, J = 15.3Hz, J = 3.4Hz), 2.45 (1H, dd, J = 15.3Hz, J = 9.3Hz),
2.52-2.94 (7H, m), 3.74 (4H, t, J = 4.4Hz), 4.02 (1H, br),
4.11 (1H, d, J = 7.3Hz), 4.22 (1H, d, J = 8.8Hz), 4.25-4.57 (3H, m), 4.71 (1H, s),
5.00 (1H, s), 5.05 (1H, t, J = 3.9Hz), 5.26 (1H, d, J = 7.3Hz),
5.35 (1H, d, J = 10.2Hz), 5.41 (1H, d, J = 10.2Hz), 5.97 (1H, t, J = 7.3Hz),
6.04 (1H, d, J = 4.4Hz), 6.25-6.40 (2H, m), 7.38 (1H, s), 7.44 (2H, t, J = 7.8Hz),
7.59 (1H, t, J = 7.8Hz), 8.07 (2H, d, J = 7.8Hz).
FAB mass ； 925 (MH+)
[0443]
Example 115
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4,10-dideacetyl-7-deoxy-4- O-Ethoxycarbonyl-9-dihydro-9,10-O- (2-dimethylaminoethylidene) baccatin III
[0444]
Melting point: 114-115 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.36 (3H, t, J = 6.9Hz), 1.41 (9H, s), 1.49 (3H, s),
1.50-2.30 (6H, m), 1.61 (3H, s), 1.78 (3H, s), 2.35-2.51 (1H, m),
2.39 (6H, m), 2.67 (1H, dd, J = 13.2Hz, J = 5.4Hz),
2.76 (1H, dd, J = 13.2Hz, J = 3.9Hz), 2.85 (1H, d, J = 4.9Hz),
4.11 (1H, d, J = 7.3Hz), 4.22 (1H, d, J = 8.8Hz), 4.23-4.57 (3H, m), 4.71 (1H, s),
4.95-5.08 (2H, m), 5.27 (1H, d, J = 7.3Hz), 5.35 (1H, d, J = 8.8Hz),
5.42 (1H, d, J = 8.8Hz), 5.98 (1H, t, J = 7.8Hz), 6.04 (1H, d, J = 4.9H),
6.23-6.39 (2H, m), 7.38 (1H, s), 7.44 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.07 (2H, d, J = 7.8Hz).
FAB mass ； 883 (MH+)
[0445]
Embedded image
[Table 6]
Example 116
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-7-deoxy-6,7-didehydro-9- Dihydro-9,10-O- (2-propenylidene) baccatin III
[0448]
Melting point: 148-151 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.40 (9H, br s), 1.52 (3H, s), 1.58 (3H, s), 1.59 (3H, s),
1.84 (1H, s), 2.14 (1H, dd, J = 7.8, J = 15.1Hz), 2.33 (3H, s),
2.44 (1H, dd, J = 9.9, J = 15.1Hz), 3.08 (1H, d, J = 5.9Hz), 3.97 (1H, d, J = 7.3Hz),
4.07-4.16 (1H, br s), 4.24 (1H, d, J = 8.1Hz), 4.34 (1H, d, J = 8.1Hz),
4.63 (1H, br s), 4.86 (1H, br d, J = 4.2Hz), 5.22 (1H, d, J = 7.3Hz),
5.26 (1H, d, J = 6.4Hz), 5.30 (1H, br d, J = 8.8Hz), 5.49 (1H, d, J = 10.7Hz),
5.61 (1H, d, J = 17.1Hz), 5.52-5.63 (1H, m), 5.70 (1H, dd, J = 10.3, J = 4.2Hz),
5.97-6.10 (3H, m), 6.11 (1H, d, J = 10.3Hz), 7.25-7.43 (5H, m),
7.48 (2H, t, J = 7.5Hz), 7.61 (1H, t, J = 7.5Hz), 8.13 (2H, d, J = 7.5Hz)
FAB mass: 830 (MH+)
[0449]
Example 117
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-7-deoxy-6,7-didehydro-9- Dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0450]
Melting point: 150-153 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23 (3H, s), 1.39 (9H, s), 1.51 (3H, s), 1.57 (3H, s), 1.64 (3H, br s),
1.84 (1H, s), 2.15 (1H, dd, J = 7.3, J = 14.8Hz), 2.32 (3H, s),
2.39 (1H, dd, J = 9.5, J = 14.8Hz), 2.55-2.70 (4H, m),
2.75 (1H, dd, J = 4.9, J = 13.7Hz), 2.82 (1H, dd, J = 3.9, J = 13.7Hz),
3.07 (1H, d, J = 5.9Hz), 3.74 (4H, t, J = 4.6Hz), 3.91 (1H, d, J = 7.6Hz),
4.00-4.15 (1H, br s), 4.24 (1H, d, J = 7.8Hz), 4.34 (1H, d, J = 7.8Hz),
4.63 (1H, br s), 4.85 (1H, d, J = 4.2Hz), 5.05 (1H, dd, J = 3.9, J = 4.9Hz),
5.15 (1H, d, J = 7.6Hz), 5.30 (1H, br d, J = 9.3Hz), 5.62 (1H, br d, J = 9.3Hz),
5.69 (1H, dd, J = 10.3, J = 4.2Hz), 5.96 (1H, d, J = 5.9Hz),
6.03-6.09 (1H, m), 6.07 (1H, d, J = 10.3Hz), 7.30-7.43 (5H, m),
7.49 (2H, t, J = 7.3Hz), 7.61 (1H, t, J = 7.3Hz), 8.13 (2H, d, J = 7.3Hz)
[0451]
Example 118
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (4-pyridyl) propionyl] -10-deacetyl-7-deoxy-6,7- Didehydro-9-dihydro-9,10-O-isopropylidenebaccatin III
[0452]
Melting point: 162-165 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.22 (3H, s), 1.41 (9H, s), 1.42 (3H, s), 1.52 (3H, s), 1.53 (3H, s),
1.57 (3H, s), 1.60 (3H, s), 1.86 (1H, s), 2.34 (3H, s), 2.05-2.17 (1H, m),
2.32-2.43 (1H, m), 3.07 (1H, d, J = 5.7Hz), 3.97 (1H, d, J = 7.3Hz),
4.22 (1H, d, J = 7.8Hz), 4.37 (1H, d, J = 7.8Hz), 4.39 (1H, br s),
4.63 (1H, br s), 4.86 (1H, d, J = 4.0Hz), 5.32 (1H, br d, J = 9.6Hz),
5.47 (1H, d, J = 7.3Hz), 5.69 (1H, dd, J = 4.0, J = 10.3Hz), 5.73 (1H, br d, J = 9.6Hz),
5.98 (1H, d, J = 5.7Hz), 6.10 (1H, d, J = 10.3Hz), 6.02-6.14 (1H, br),
7.36 (2H, d, J = 5.9Hz), 7.48 (2H, t, J = 7.4Hz), 7.61 (1H, t, J = 7.4Hz),
8.14 (2H, d, J = 7.4Hz), 8.60 (2H, d, J = 5.9Hz)
FAB mass: 833 (MH+)
[0453]
Example 119
9 β-4-O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -7-deoxy-4, 10-dideacetyl-6,7-didehydro-9-dihydro-9,10-O- (2-propenylidene) baccatin III
[0454]
Melting point: 127-130 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23-1.29 (3H, m), 1.41 (9H, s), 1.53 (3H, s), 1.60 (6H, s), 1.70 (3H, s),
1.77-1.92 (2H, m), 2.27 (1H, dd, J = 8.3, J = 15.3Hz),
2.39 (1H, dd, J = 9.5, J = 15.3Hz), 2.44-2.70 (2H, m), 3.12 (1H, d, J = 5.9Hz),
3.76 (1H, br s), 4.01 (1H, d, J = 7.3Hz), 4.27 (1H, d, J = 8.3Hz),
4.34 (1H, d, J = 8.3Hz), 4.71 (1H, br d, J = 3.9Hz), 4.81 (1H, d, J = 4.2Hz),
5.22 (1H, d, J = 7.3Hz), 5.25 (1H, d, J = 6.4Hz), 5.33 (2H, br s),
5.48 (1H, d, J = 10.7Hz), 5.60 (1H, d, J = 17.1Hz),
5.70 (1H, dd, J = 10.3, J = 4.2Hz), 5.99 (1H, d, J = 5.9Hz),
6.00-6.13 (2H, m), 6.12 (1H, d, J = 10.3Hz), 6.34 (1H, d, J = 2.9Hz),
6.35-6.38 (1H, m), 7.40 (1H, br s), 7.49 (2H, t, J = 7.3Hz),
7.62 (1H, t, J = 7.3Hz), 8.16 (2H, d, J = 7.3Hz)
[0455]
Example 120
9 β-4-O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -7-deoxy-4, 10-dideacetyl-6,7-didehydro-9-dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0456]
Melting point: 132-135 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.01 (3H, t, J = 7.3Hz), 1.25 (3H, s), 1.40 (9H, s), 1.52 (3H, s), 1.56 (3H, s),
1.68 (3H, s), 1.78-1.90 (2H, m), 2.28 (1H, dd, J = 8.3, J = 14.9Hz),
2.39 (1H, dd, J = 9.5, J = 14.9Hz), 2.44-2.55 (1H, m), 2.55-2.70 (5H, m),
2.76 (1H, dd, J = 13.7, J = 5.1Hz), 2.81 (1H, dd, J = 13.7, J = 3.9Hz),
3.10 (1H, d, J = 6.2Hz), 3.75 (4H, t, J = 4.7Hz), 3.97 (1H, d, J = 7.5Hz),
4.26 (1H, d, J = 8.3Hz), 4.33 (1H, d, J = 8.3Hz), 4.71 (1H, br s),
4.81 (1H, d, J = 3.9Hz), 5.04 (1H, dd, J = 5.1, J = 3.9Hz), 5.16 (1H, d, J = 7.5Hz),
5.32 (2H, br s), 5.70 (1H, dd, J = 10.3, J = 3.9Hz), 5.96 (1H, d, J = 6.2Hz),
6.03-6.13 (1H, m), 6.09 (1H, d, J = 10.3Hz), 6.30-6.40 (2H, m), 7.40 (1H, s),
7.50 (2H, t, J = 7.3Hz), 7.62 (1H, t, J = 7.3Hz), 8.16 (2H, d, J = 7.3Hz)
[0457]
Example 121
9 β-13-O- [3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -4-O-cyclopropanecarbonyl-7-deoxy-4, 10-dideacetyl-6,7-didehydro-9-dihydro-9,10-O-isopropylidenebaccatin III
[0458]
Melting point: 165-168 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (s), 1.38 (s), 1.42 (s), 1.51 (s), 1.57 (s), 1.59 (s), 2.20 (1H, m),
2.28 (1H, m), 3.11 (1H, d, J = 5Hz), 3.94 (1H, d, J = 7.5Hz), 4.14 (1H, d, J = 8Hz),
4.33 (1H, d, J = 8Hz), 4.54 (1H, br), 4.75 (1H, d, J = 4Hz), 5.00 (1H, d, J = 9.5Hz),
5.45 (1H, d, J = 7.5Hz), 5.67 (1H, dd, J = 10Hz, J = 4Hz), 5.85 (1H, d, J = 9.5Hz),
6.00 (1H, d, J = 5Hz), 6.07 (1H, d, J = 10Hz), 6.18 (1H, t-br),
7.34 (2H, d, J = 5.5Hz), 7.50 (2H, t, J = 7.5Hz), 7.62 (1H, t, J = 7.5Hz),
8.07 (2H, d, J = 7.5Hz), 8.57 (2H, d, J = 5.5Hz).
FAB mass ： 873 (M+).
[0459]
Example 122
9 β-13-O- [3- (tert-Butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-pyridyl) propionyl] -10-deacetyl-7-deoxy-6,7-didehydro- 9-Dihydro-9,10-O-isopropylidenebaccatin III
[0460]
Melting point: 161-164 ℃ (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (s), 1.34 (9H, s), 1.42 (s), 1.54 (s), 1.58 (s), 1.59 (s), 2.22 (2H, m),
2.52 (3H, s), 3.10 (1H, d, J = 5.5Hz), 3.98 (1H, d, J = 7.5Hz),
4.24 (1H, d, J = 8Hz), 4.38 (1H, d, J = 8Hz), 4.85 (1H, d, J = 4Hz),
5.02 (1H, d, J = 10Hz), 5.44 (1H, d, J = 7.5Hz), 5.69 (1H, dd, J = 10Hz, J = 4Hz),
5.74 (1H, d, J = 10Hz), 5.96 (1H, d, J = 5.5Hz), 6.10 (1H, d, J = 10Hz),
6.23 (1H, t, J = 9Hz), 7.35 (2H, d, J = 5Hz), 7.49 (2H, t, J = 7.5Hz),
7.61 (1H, t, J = 7.5Hz), 8.15 (2H, d, J = 7.5Hz), 8.60 (2H, d, J = 5Hz).
FAB mass ： 847 (M+).
[0461]
Example 123
9 β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-O-cyclopropanecarbonyl-7-deoxy- 4,10-dideacetyl-6,7-didehydro-9-dihydro-9,10-O- (2-morpholinoethylidene) baccatin III
[0462]
Melting point: 105-110 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (7H, s like), 1.41 (9H, s), 1.50 (3H, s), 1.56 (3H, s), 1.71 (3H, s),
2.33-2.44 (3H, m), 2.64 (4H, m), 2.79 (2H, AB type q, J = 8.3Hz),
3.10 (1H, d, J = 5.9Hz), 3.72-7.76 (4H, m), 3.94 (1H, d, J = 7.3Hz),
4.25 (2H, AB type q, J = 8.3Hz), 4.73 (1H, s), 4.78 (1H, d, J = 4.4Hz),
5.05 (1H, dd, J = 4.9Hz, J = 3.9Hz), 5.45 (1H, d, J = 17.2Hz),
5.69 (1H, dd, J = 10.3Hz, J = 3.9Hz), 5.98 (1H, d, J = 5.9Hz), 6.04 (1H, m),
6.07 (1H, d, J = 10.7Hz), 6.32 (1H, d, J = 3.4Hz),
6.35 (1H, dd, J = 3.4Hz, J = 2.0Hz), 7.36 (1H, s), 7.50 (2H, t, J = 7.3Hz),
7.62 (1H, t, J = 7.3Hz), 8.10 (2H, d, J = 7.3Hz).
FAB mass ： 919 (MH+).
[0463]
Example 124
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy- (2-pyridyl) propionyl] -10-deacetyl-7-deoxy-6,7-didehydro- 9-Dihydro-9,10-O-isopropylidenebaccatin III
[0464]
Melting point: 143-148 ° C (freeze-dried from dioxane)
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.24 (3H, s), 1.41 (3H, s), 1.43 (9H, s), 1.55 (3H, s), 1.59 (3H, s),
1.60 (3H, s), 1.66 (3H, s), 1.80 (1H, s), 2.23-2.38 (2H, m), 2.42 (3H, s),
3.12 (1H, d, J = 5.9Hz), 4.06 (1H, d, J = 7.6Hz), 4.28 (1H, d, J = 8.3Hz),
4.33 (1H, d, J = 8.3Hz), 4.78 (1H, br s), 4.87 (1H, br s),
4.88 (1H, d, J = 4.2Hz), 5.35 (1H, br d, J = 9.8Hz), 5.47 (1H, d, J = 7.8Hz),
5.68 (1H, dd, J = 4.2, J = 10.6Hz), 5.91 (1H, d, J = 9.8Hz), 5.94 (1H, d, J = 5.9Hz),
6.09 (1H, d, J = 10.6Hz), 6.05-6.15 (1H, m), 7.20-7.28 (1H, m),
7.41 (1H, d, J = 7.8Hz), 7.48 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz),
7.73 (1H, d, J = 7.8Hz), 8.14 (2H, d, J = 7.3Hz), 8.52 (1H, d, J = 4.4Hz)
[0465]
Embedded image
[Table 7]
Example 125
9 β-4-O-butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -7-deoxy-4, 10-dideacetyl-9-dihydro-7β, 8β-methylene-9,10-O- (2-morpholinoethylidene) -19-norbaccatin III
[0468]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.74 (1H, br t, J = 5.0Hz), 0.99 (3H, t, J = 7.6Hz), 1.18-1.80 (9H, m),
1.20 (3H, s), 1.35 (9H, s), 1.53 (3H, s), 2.29 (1H, dd, J = 8.8, J = 15.6Hz),
2.40-2.77 (10H.m), 3.12 (1H, d, J = 8.3Hz), 3.36 (1H, br s),
3.72 (4H, t, J = 4.6Hz), 4.13 (1H, dd, J = 7.8, J = 2.6Hz), 4.32 (1H, d, J = 7.8Hz),
4.47-4.55 (2H, m), 4.67 (1H, br s), 4.91 (1H, t, J = 4.4Hz),
5.09 (1H, d, J = 7.3Hz), 5.24 (1H, d, J = 9.7Hz), 5.38 (1H, br d, J = 9.7Hz),
5.52 (1H, d, J = 8.3Hz), 6.22 (1H, br t, J = 8.8Hz), 6.35 (1H, d, J = 2.9Hz),
6.39 (1H, dd, J = 2.9, J = 1.5Hz), 7.42 (1H, d, J = 1.5Hz), 7.49 (2H, t, J = 7.8Hz),
7.57 (1H, t, J = 7.8Hz), 8.08 (2H, d, J = 7.8Hz)
[0469]
Example 126
9 β-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetyl-7-deoxy-9-dihydro-7β, 8β- Methylene-9,10-O- (2-morpholinoethylidene) -19-norbaccatin III
[0470]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.77 (1H, br s), 1.10-1.80 (3H, m), 1.21 (3H, s), 1.34 (9H, s), 1.54 (3H, s),
1.68 (3H, s), 1.75 (1H, s), 2.23 (3H, s), 2.31 (1H, dd, J = 8.8, J = 15.6Hz),
2.50-2.78 (8H.m), 3.12 (1H, d, J = 8.3Hz), 3.48 (1H, br s),
3.72 (4H, t, J = 4.6Hz), 4.17 (1H, dd, J = 7.8, J = 2.0Hz), 4.32-4.48 (2H, m),
4.54 (1H, t, J = 8.8Hz), 4.60 (1H, br s), 4.91 (1H, t, J = 4.2Hz),
5.09 (1H, d, J = 7.3Hz), 5.31 (1H, br d, J = 9.1Hz), 5.47 (1H, d, J = 9.1Hz),
5.53 (1H, d, J = 8.3Hz), 6.20 (1H, br t, J = 8.3Hz), 7.30-7.43 (5H, m),
7.49 (2H, t, J = 7.8Hz), 7.57 (1H, t, J = 7.8Hz), 8.08 (2H, d, J = 7.8Hz)
[0471]
Reference example 1
[0472]
Embedded image
Step 1: 9β-10-deacetyl-13-deoxy-9-dihydro-9,10-O-isopropylidene-13-oxobaccatin III
0.1301 g of the compound obtained in Step 2 of Example 1 was dissolved in 6.5 ml of dioxane, 0.823 g of manganese dioxide was added at room temperature, and the mixture was vigorously stirred at room temperature for 15 hours. The reaction solution was filtered through Celite, the filtrate was washed with chloroform, and the solvent of the filtrate was distilled off under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: acetone = 10: 1 (v / v)) to obtain 0.1154 g of the title compound as a colorless transparent syrupy substance.
[0474]
Rf = 0.60 (chloroform: acetone = 10: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.27 (3H, s), 1.43 (3H, s), 1.61 (3H, s), 1.66 (3H, s), 1.68 (3H, s),
1.94 (3H, s), 2.01 (1H, s), 2.17 (2H, m), 2.22 (3H, s),
2.64 (1H, AB type d, J = 20.0Hz), 2.90 (1H, AB type d, J = 20.0Hz),
3.15 (1H, d, J = 4.4Hz), 3.99 (1H, d, J = 7.3Hz), 4.07 (1H, m),
4.24 (1H, AB type d, J = 7.8Hz), 4.65 (1H, AB type d, J = 7.8Hz),
4.41 (1H, dd, J = 1.5Hz, 8.8Hz), 5.04 (1H, s), 5.68 (1H, d, J = 7.3Hz),
6.16 (1H, d, J = 4.8Hz), 7.49 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.11 (2H, d, J = 7.8Hz).
[0475]
Step 2: 9β-10-deacetyl-13-deoxy-9-dihydro-9,10-O-isopropylidene-13-oxo-7-O-triethylsilylbaccatin III
73.0 mg of the compound obtained in the above step 1 was dissolved in 2.2 ml of methylene chloride, and 0.075 ml of 2,6-lutidine and 0.112 ml of triethylsilyl trifluoromethanesulfonate were added at -32 ° C. After 30 minutes, saturated aqueous sodium hydrogen carbonate was added at −30 ° C., extracted with chloroform, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; chloroform: methanol = 8.5: 1 (v / v)) to obtain 48.3 mg of the title compound as a white solid.
[0476]
Rf = 0.40 (Hexane: Ethyl acetate = 7: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.60 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8Hz), 1.24 (3H, s), 1.44 (3H, s),
1.54 (3H, s), 1.61 (3H, s), 1.67 (3H, s), 1.94 (3H, s), 2.21 (3H, s),
1.98-2.13 (2H, m), 2.62 (1H, AB type d, J = 20.0Hz),
2.93 (1H, AB type d, J = 20.0Hz), 3.23 (1H, d, J = 5.4Hz), 4.07 (1H, t, J = 2.9Hz),
4.21 (1H, AB type d, J = 7.8Hz), 4.43 (1H, AB type d, J = 7.8Hz),
4.30 (1H, b, d), 4.78 (1H, t, J = 4.0Hz), 5.61 (1H, d, J = 7.8Hz),
6.07 (1H, d, J = 5.4Hz), 6.94 (1H, d, J = 7.8Hz), 7.49 (2H, t, J = 7.8Hz),
7.60 (1H, t, J = 7.8Hz), 8.12 (2H, d, J = 7.8Hz).
[0477]
Step 3: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
48.3 mg of the compound obtained in the above step 2 was dissolved in a mixed solvent of tetrahydrofuran-methanol (20: 1 (v / v)), and 11.0 mg of sodium borohydride was added at room temperature. After 1.5 hours, the mixture was neutralized with a saturated aqueous ammonium chloride solution at 0 ° C., and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, 48.3 mg of the resulting residue was dissolved in 2.5 ml of methylene chloride, 1.0N diisobutylaluminum hydride (toluene solution, 0.17 ml) was added dropwise at -82 ° C, and the mixture was stirred for 10 minutes. Methanol was added at −78 ° C., an aqueous solution of Rochelle salt (0.23 g) (water 1.5 ml) was added, and the mixture was vigorously stirred at room temperature for 1 hour. The mixture was extracted with chloroform, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 2: 1 (v / v)) to give 10.8 mg of the title compound as a colorless transparent syrup. Obtained as material.
[0478]
Rf = 0.49 (hexane: ethyl acetate = 2: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.61 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8Hz), 1.12 (3H, s), 1.40 (3H, s),
1.49 (3H, s), 1.56 (3H, s), 1.57 (3H, s), 1.93 (3H, s), 1.95-2.11 (3H, m),
2.26-2.44 (2H, m), 2.32 (3H, s), 3.16 (1H, d, J = 4.9Hz), 4.06 (1H, t, J = 4.8Hz),
4.21 (1H, AB type d, J = 7.8Hz), 4.54 (1H, AB type d, J = 7.8Hz),
4.72-4.84 (2H, m), 5.51 (1H, d, J = 7.8Hz), 5.91 (1H, d, J = 4.9Hz),
7.48 (2H, t, J = 7.3Hz), 7.59 (1H, t, J = 7.3Hz), 8.13 (2H, d, J = 7.3Hz).
[0479]
Step 4: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyloxy) propionyl] -10-deacetyl-9 -Dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
The compound obtained in Step 3 above and (3R, 4R) -1- (tert-butoxycarbonyl) -4- (2-furyl) -3- (triisopropylsilyloxy) azetidin-2-one were used in the steps of Example 1. Reaction as in 3 and purification gave the title compound.
[0480]
Rf = 0.25 (hexane: ethyl acetate = 6: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.62 (6H, q, J = 7.8Hz), 0.85-1.01 (30H, m), 1.06 (3H, s), 1.23 (3H, s),
1.38 (9H, s), 1.46 (6H, s), 1.50 (3H, s), 1.76 (3H, s), 2.04-2.29 (3H, m),
2.43 (3H, s), 2.36-2.45 (1H, m), 3.16 (1H, d, J = 5.4Hz),
3.98 (1H, dd, J = 8.4Hz, 3.2Hz), 4.25 (1H, d, J = 8.0Hz), 4.40-4.48 (1H, m),
4.50 (1H, d, J = 8.0Hz), 4.83 (1H, t, J = 6.8Hz), 4.96 (1H, s), 5.25-5.36 (2H, m),
5.41 (1H, d, J = 4.8Hz), 5.89 (1H, d, J = 5.4Hz), 6.12 (1H, t),
6.24 (1H, d, J = 3.2Hz), 6.34 (1H, d, J = 3.2Hz), 7.36 (1H, s),
7.48 (2H, t, J = 7.2Hz), 7.57 (1H, t, J = 7.2Hz), 8.11 (2H, d, J = 7.2Hz).
[0481]
Step 5: 9β-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetyl-9-dihydro-9, 10-O-isopropylidenebaccatin III
The compound obtained in Step 3 above was reacted in the same manner as in Step 4 of Example 1 to obtain the same title compound as the compound obtained in Step 4 of Example 1.
[0482]
Reference example 2
[0483]
Embedded image
9β-4-O-butanoyl-4,10-dideacetyl-13-deoxy-9-dihydro-9,10-O-isopropylidene-13-oxobaccatin III
84.9 mg of the compound obtained in Step 1 of Reference Example 1 was dissolved in 2.9 ml of tetrahydrofuran, and 0.73 ml of 1N sodium hexamethyldisilazide (tetrahydrofuran solution) was added dropwise at -58 ° C. After 5 minutes, 0.058 ml of ethyl iodide Was added. After 1.5 hours, a saturated aqueous ammonium chloride solution was poured at -52 ° C, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 5: 2 (v / v)) to give 19.1 mg of the title compound as a colorless transparent syrup. Obtained as material.
[0485]
Rf = 0.23 (hexane: ethyl acetate = 5: 2 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.06 (3H, t, J = 7.3Hz), 1.26 (3H, s), 1.43 (3H, s), 1.61 (3H, s), 1.67 (3H, s),
1.68 (3H, s), 1.68-1.80 (2H, m), 1.93 (3H, s), 1.97 (1H, s),
2.12-2.23 (2H, m), 2.38-2.54 (2H, m), 2.62 (1H, AB type d, J = 19.5Hz),
2.89 (1H, AB type d, J = 19.5Hz), 3.17 (1H, d, J = 4.4Hz), 3.99 (1H, d, J = 7.3Hz),
4.05-4.11 (1H, m), 4.24 (1H, AB type d, J = 8.8Hz),
4.67 (1H, AB type d, J = 8.8Hz), 4.42 (1H, dd, J = 8.3Hz, 0.9Hz), 5.00 (1H, s),
5.67 (1H, d, J = 7.3Hz), 6.15 (1H, d, J = 4,4Hz), 7.49 (2H, t, J = 8.3Hz),
7.62 (1H, t, J = 8.3Hz), 8.11 (2H, d, J = 8.3Hz).
[0486]
Reference example 3
[0487]
Embedded image
9β-4-O-butanoyl-4,10-dideacetyl-13-deoxy-9-dihydro-9,10-O-isopropylidene-13-oxo-7-O-triethylsilylbaccatin III
Using the compound obtained in Step 2 of Reference Example 1 as a raw material, the same operation as in Reference Example 2 was performed to obtain the title compound as a colorless transparent syrup-like substance.
[0489]
Rf = 0.33 (hexane: ethyl acetate = 4: 1 (v / v))
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.60 (6H, q, J = 8.0Hz), 0.94 (9H, t, J = 8.0Hz), 1.05 (3H, t, J = 7.6Hz),
1.22 (3H, s), 1.43 (3H, s), 1.53 (3H, s), 1.61 (3H, s), 1.65 (3H, s),
1.66-1.82 (2H, m), 1.93 (3H, s), 1.98-2.13 (2H, m), 2.32-2.53 (2H, m),
2.59 (1H, AB type d, J = 19.5Hz), 2.91 (1H, AB type d, J = 19.5Hz),
3.22 (1H, d, J = 4.8Hz), 4.08 (1H, t, J = 4.0Hz), 4.21 (1H, AB type d, J = 7.7Hz),
4.44 (1H, AB total d, J = 7.7Hz), 4.24-4.35 (1H, m), 4.74 (1H, t, J = 4.0Hz),
5.61 (1H, d, J = 7.5Hz), 6.07 (1H, d, J = 4.8Hz), 7.48 (2H, t, J = 7.7Hz),
7.61 (1H, t, J = 7.7Hz), 8.13 (2H, d, J = 7.7Hz).
FAB mass: 838 (MH+).
[0490]
Reference example 4
[0491]
Embedded image
Step 1: 13-O-benzyloxycarbonyl-10-deacetyl-7,10-bis-O- (2,2,2-trichloroethoxycarbonyl) baccatin III
2.409 g of 10-deacetyl-7,10-bis-O- (2,2,2-trichloroethoxycarbonyl) baccatin III was dissolved in 15 ml of dry tetrahydrofuran and 0.92 g of benzyl was cooled to −50 ° C. Oxycarbonyl chloride was added, followed by dropwise addition of 5.38 ml of 1N sodium hexamethyldisilazide (tetrahydrofuran solution), and the mixture was stirred at that temperature for 3 hours. Aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane containing 10% (v / v) ethyl acetate, changed from the middle to 15%, and further changed to 20%). 1.607 g of compound was obtained as a colorless glassy solid.
[0493]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.18 (3H, s), 1.19 (3H, s), 1.84 (3H, s), 2.0-2.2 (1H, m), 2.06 (1H, d, J = 1Hz),
2.28 (3H, s), 2.35 (2H, m), 2.62 (1H, ddd, J = 15Hz, 9Hz, 7Hz),
3.94 (1H, d, J = 7Hz), 4.13 (1H, d, J = 8Hz), 4.32 (1H, d, J = 8Hz),
4.60 (1H, d, J = 12Hz), 4.76 (1H, AB type d, J = 12Hz),
4.79 (1H, AB type d, J = 12Hz), 4.91 (1H, d, J = 12Hz), 4.96 (1H, d, J = 8Hz),
5.25 (2H, s), 5.60 (1H, dd, J = 11Hz, 7Hz), 5.66 (1H, d, J = 7Hz),
5.95 (1H, t, J = 8Hz), 6.26 (1H, s), 7.40 (5H, s), 7.48 (2H, t, J = 7.5Hz),
7.62 (1H, t, J = 7.5Hz), 8.07 (2H, m).
[0494]
Step 2: 13-O-benzyloxycarbonyl-10-deacetylbaccatin III
The compound obtained in Step 1 was reacted in the same manner as in Step 3 of Example 9 to obtain the title compound.
[0495]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.11 (3H, s), 1.16 (3H, s), 1.74 (3H, s), 1.82 (1H, m), 1.97 (3H, s),
2.25 (3H, s), 2.32 (2H, m), 2.59 (1H, ddd, J = 14Hz, 9.5Hz, 6.5Hz),
3.96 (1H, d, J = 7Hz), 4.16 (2H, m), 4.30 (2H, m), 4.95 (1H, d, J = 8Hz),
5.24 (3H, m), 5.65 (1H, d, J = 7Hz), 5.92 (1H, t, J = 8Hz), 7.40 (5H, s),
7.48 (2H, t, J = 7.5Hz), 7.62 (1H, t, J = 7.5Hz), 8.07 (2H, m).
[0496]
Step 3: 9β-13-O-benzyloxycarbonyl-10-deacetyl-9-dihydrobaccatin III
119 mg of the compound obtained in Step 2 above was dissolved in 10 ml of dry methylene chloride, 180 mg of tetrabutylammonium borohydride was added at room temperature, and the mixture was stirred at room temperature for 15 hours. 1N hydrochloric acid was added to the reaction solution and stirred until no bubbles appeared. The organic layer was taken, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was dissolved in methanol and allowed to stand for 3 hours. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform containing 6% (v / v) methanol) to obtain 86 mg of the title compound as a white powder. .
[0497]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.25 (3H, s), 1.64 (3H, s), 1.75 (3H, s), 1.80 (3H, s), 1.91 (1H, m),
2.19 (3H, s), 2.29 (2H, m), 2.49 (1H, m), 3.08 (1H, d, J = 5Hz), 4.11 (1H, br),
4.16 (1H, d, J = 8Hz), 4.34 (2H, m), 4.98 (1H, d, J = 7Hz),
5.17 (2H, d and br, J = 12Hz), 5.27 (1H, d, J = 12Hz), 5.96 (1H, t, J = 8Hz),
6.09 (1H, d, J = 5Hz), 7.39 (5H, m), 7.46 (2H, t, J = 7.5Hz),
7.58 (1H, t, J = 7.5Hz), 8.08 (2H, d, J = 7.5Hz).
[0498]
Step 4: 9β-13-O-benzyloxycarbonyl-10-deacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
The compound obtained in Step 3 was reacted in the same manner as in Step 2 of Example 1 to obtain the title compound as a glassy solid.
[0499]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.23 (3H, s), 1.40 (3H, s), 1.57 (3H, s), 1.63 (3H, s), 1.65 (3H, s),
1.79 (3H, s), 2.18 (2H, m), 2.23 (3H, s), 2.30 (2H, m), 2.97 (1H, d, J = 5Hz),
3.89 (1H, d, J = 7.5Hz), 4.03 (1H, m), 4.26 (1H, d, J = 8Hz), 4.38 (1H, d, J = 8Hz),
4.66 (1H, d, J = 8Hz), 5.09 (1H, br), 5.18 (1H, d, J = 12Hz), 5.26 (1H, d, J = 12Hz),
5.55 (1H, d, J = 7.5Hz), 5.92 (1H, t, J = 8Hz), 5.99 (1H, d, J = 5Hz), 7.39 (5H, m),
7.46 (2H, t, J = 7.5Hz), 7.59 (1H, t, J = 7.5Hz), 8.09 (2H, d, J = 7.5Hz).
[0500]
Step 5: 9β-13-O-benzyloxycarbonyl-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
The compound obtained in Step 3 was reacted in the same manner as in Step 2 of Example 3 to obtain the title compound as a glassy solid.
[0501]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.62 (6H, q, J = 8Hz), 0.97 (9H, t, J = 7Hz), 1.15 (3H, s), 1.38 (3H, s),
1.47 (3H, s), 1.51 (3H, s), 1.79 (3H, d, J = 1Hz), 2.08 (1H, m), 2.24 (3H, s),
2.28-2.39 (3H, m), 3.21 (1H, d, J = 6Hz), 3.94 (1H, dd, J = 10Hz, 4Hz),
4.27 (1H, d, J = 8Hz), 4.46 (1H, d, J = 8Hz), 4.54 (1H, br), 4.80 (1H, t, J = 7Hz),
5.19 (1H, d, J = 12Hz), 5.25 (1H, d, J = 12Hz), 5.42 (1H, d, J = 9Hz),
5.84 (1H, d, J = 6Hz), 5.88 (1H, t, J = 10Hz), 7.39 (5H, m), 7.46 (2H, t, J = 7.5Hz),
7.59 (1H, t, J = 7.5Hz), 8.08 (2H, d, J = 7.5Hz).
[0502]
Step 6: 9β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
122 mg of the compound obtained in the above step 5 was dissolved in 10 ml of ethanol, 40 mg of 10% palladium carbon was added, and the mixture was stirred for 1 hour in a hydrogen atmosphere. Insoluble matters were removed by filtration, and the solvent of the filtrate was distilled off under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; chloroform containing 5% (v / v) acetone), and 80 mg of the same title compound as that obtained in Step 3 of Example 3 was obtained. Obtained.
[0503]
Reference Example 5
[0504]
Embedded image
9 β-10-deacetyl-9-dihydro-9,10-O- (2-propenylidene) -7-O- triethylsilylbaccatin III
9 Dissolve 0.4030 g of β-10-deacetyl-9-dihydro-9,10-O- (2-propenylidene) baccatin III in 80 ml of methylene chloride and add 0.232 ml of 2,6-di-tert-butylpyridine at room temperature. After addition and cooling to -78 ° C, 0.202 ml of triethylsilyl trifluoromethanesulfonate was added dropwise. After 16 minutes, methanol and saturated aqueous sodium hydrogen carbonate solution were added at −78 ° C., extracted with chloroform, and washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (developing solvent; hexane: ethyl acetate = 20: 1 (v / v) → chloroform: acetone = 7: 1 (v / v)) to give 0.4126 g of the title compound as a white foam.
[0506]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.58-0.71 (6H, m), 0.98 (9H, t, J = 7.8Hz), 1.09 (3H, s), 1.56 (3H, s),
1.60 (3H, s), 1.75 (1H, s), 1.94 (3H, s), 2.00-2.45 (4H, m), 2.30 (3H, s),
3.19 (1H, d, J = 5.3Hz), 3.95 (1H, dd, J = 8.8Hz, J = 5.8Hz), 4.32 (1H, d, J = 8.3Hz),
4.35 (1H, d, J = 8.3Hz), 4.61 (1H, d, J = 7.8Hz), 4.72-4.89 (2H, m),
5.09 (1H, d, J = 5.8Hz), 5.33 (1H, d, J = 7.8Hz), 5.46 (1H, d, J = 10.7Hz),
5.56 (1H, d, J = 17.1Hz), 5.90 (1H, d, J = 5.3Hz),
6.16 (1H, ddd, J = 17.1Hz, J = 10.7Hz, J = 5.8Hz), 7.47 (2H, t, J = 7.3Hz),
7.59 (1H, t, J = 7.3Hz), 8.11 (2H, d, J = 7.3Hz).
[0507]
Reference Example 6
[0508]
Embedded image
9 β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
9 β-10-deacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III was used as a raw material, and the title compound was obtained in the same manner as in Step 1 of Reference Example 5.
[0510]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.61 (6H, q, J = 7.8Hz), 0.96 (9H, t, J = 7.8Hz), 1.11 (3H, s), 1.40 (3H, s),
1.50 (3H, s), 1.57 (3H, s), 1.59 (3H, s), 1.93 (3H, s), 1.88-2.15 (2H, m),
2.23-2.47 (2H, m), 2.32 (3H, s), 3.16 (1H, d, J = 5.3Hz), 4.17 (1H, t, J = 4.8Hz),
4.17-4.29 (1H, m), 4.20 (1H, d, J = 7.8Hz), 4.54 (1H, d, J = 7.8Hz),
4.73-4.88 (2H, m), 5.51 (1H, d, J = 7.8Hz), 5.91 (1H, d, J = 5.3Hz),
7.48 (2H, t, J = 7.3Hz), 7.59 (1H, t, J = 7.3Hz), 8.14 (2H, t, J = 7.3Hz).
[0511]
Reference Example 7
[0512]
Embedded image
Step 1: 9 β-10-deacetyl-9-dihydro-9,10-O- (2-propenylidene) -7,13-bis-O-triethylsilylbaccatin III
Dissolve 2.115 g of the compound obtained in Step 1 of Reference Example 5 in 150 ml of methylene chloride, add 0.528 ml of 2,6-lutidine at room temperature, cool to −58 ° C., and then add 0.88 ml of triethylsilyl trifluoromethanesulfonate. It was dripped. After 40 minutes, 0.176 ml of 2,6-lutidine and 0.293 ml of triethylsilyl trifluoromethanesulfonate were added at -52 ° C. Methanol and a saturated aqueous sodium hydrogen carbonate solution were added at −52 ° C., and the mixture was extracted with chloroform and washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 6: 1 (v / v)) to give the title compound 1.7763 g was obtained as a white foam.
[0514]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.55-0.73 (6H, m), 0.99 (9H, t, J = 7.8Hz), 1.01 (9H, t, J = 7.8Hz), 1.14 (3H, s),
1.52 (3H, s), 1.53 (3H, s), 1.72 (1H, s), 1.87 (3H, s), 2.01-2.16 (2H, m),
2.26 (3H, s), 3.21 (1H, d, J = 5.9Hz), 3.92 (1H, dd, J = 10.7Hz, J = 5.3Hz),
4.32 (1H, d, J = 8.3Hz), 4.39 (1H, d, J = 8.3Hz), 4.59 (1H, d, J = 9.3Hz),
4.83 (1H, dd, J = 8.7Hz, J = 5.3Hz), 4.94 (1H, t, J = 7.3Hz), 5.05 (1H, d, J = 5.9Hz),
5.30 (1H, d, J = 9.3Hz), 5.44 (1H, d, J = 10.7Hz), 5.82 (1H, d, J = 5.9Hz),
6.12 (1H, ddd, J = 17.6Hz, J = 10.7Hz, J = 5.9Hz), 7.46 (2H, t, J = 7.3Hz),
7.57 (1H, t, J = 7.3Hz), 8.08 (2H, d, J = 7.3Hz).
[0515]
Step 2: 9 β-4-O-butanoyl-4,10-dideacetyl-9-dihydro-9,10-O- (2-propenylidene) -7,13-bis-O-triethylsilylbaccatin III
Dissolve 0.7671 g of the compound obtained in Step 1 above in 37 ml of dry tetrahydrofuran, add 4.7 ml of sodium bistrimethylsilylamide (1.0 mol / L tetrahydrofuran solution) dropwise at 0 ° C, and add 0.37 ml of ethyl iodide after 15 minutes. The mixture was stirred at that temperature for 30 minutes. Saturated aqueous ammonium chloride solution was added at 0 ° C., diluted with ethyl acetate, and the mixture was separated and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 7: 1 (v / v)) to obtain 0.2604 g of the title compound as a white glassy substance.
[0516]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.58-0.73 (12H, m), 0.93-1.10 (21H, m), 1.15 (3H, s), 1.52 (3H, s),
1.53 (3H, s), 1.70 (1H, s), 1.74-1.90 (2H, m), 1.85 (3H, s),
2.01-2.12 (2H, m), 2.17-2.30 (1H, m), 2.32-2.43 (1H, m), 2.45-2.63 (2H, m),
3.19 (1H, d, J = 5.9Hz), 3.93 (1H, dd, J = 11.3Hz, J = 5.4Hz),
4.32 (1H, d, J = 8.3Hz), 4.39 (1H, d, J = 8.3Hz), 4.58 (1H, d, J = 8.8Hz),
4.79 (1H, dd, J = 8.8Hz, J = 4.9Hz), 4.94 (1H, t, J = 8.3Hz), 5.05 (1H, d, J = 5.9Hz),
5.29 (1H, d, J = 8.8Hz), 5.44 (1H, d, J = 10.8Hz), 5.55 (1H, d, J = 17.6Hz),
5.81 (1H, d, J = 5.9Hz), 6.11 (1H, ddd, J = 17.6Hz, J = 10.8Hz, J = 5.9Hz),
7.46 (2H, t, J = 7.8Hz), 7.58 (1H, t, J = 7.8Hz), 8.09 (2H, d, J = 7.8Hz).
[0517]
Step 3: 9 β-4-O-butanoyl-4,10-dideacetyl-9-dihydro-9,10-O- (2-propenylidene) baccatin III
0.1414 g of the compound obtained in the above step 2 was dissolved in 7.0 ml of pyridine, and 1.41 ml of hydrogen fluoride pyridine was gradually added dropwise at 0 ° C. After completion of dropping, the mixture was stirred at room temperature for 14 hours. Cold water was added at 0 ° C., and the mixture was diluted with ethyl acetate, separated, and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (developing solvent; chloroform: acetone = 7: 1 (v / v)) to obtain 69.7 mg of the title compound as a white glassy substance.
[0518]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.06 (3H, s), 1.16 (3H, s), 1.62 (3H, s), 1.65 (3H, s), 1.73-1.86 (2H, m),
1.90-2.00 (1H, m), 1.93 (3H, s), 2.10-2.29 (3H, m),
2.34 (1H, dd, J = 15.6Hz, J = 9.7Hz), 2.60 (2H, t, J = 7.8Hz),
3.05 (1H, d, J = 4.9Hz), 3.88 (1H, d, J = 6.8Hz), 4.06-4.18 (1H, m),
4.33 (1H, d, J = 8.4Hz), 4.40 (1H, dd, J = 8.4Hz, J = 1.5Hz), 4.59 (1H, d, J = 8.3Hz),
4.78 (1H, br q, J = 7.4Hz), 5.02 (1H, s), 5.22 (1H, d, J = 5.9Hz),
5.30 (1H, d, J = 6.8Hz), 5.44 (1H, d, J = 10.8Hz), 5.56 (1H, d, J = 17.1Hz),
5.95-6.13 (2H, m), 7.48 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.14 (2H, d, J = 7.8Hz).
[0519]
Step 4: 9 β-4-O-butanoyl-4,10-dideacetyl-9-dihydro-9,10-O- (2-propenylidene) -7-O- triethylsilylbaccatin III
The title compound was obtained by carrying out the same reaction operation as in step 1 of Reference Example 5 using the compound obtained in the above step 3 as a raw material.
[0520]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.64 (6H, q like, J = 7.8Hz), 0.98 (9H, t, J = 7.8Hz), 1.05 (3H, s), 1.41 (3H, s),
1.56 (3H, s), 1.61 (3H, s), 1.71-1.84 (2H, m), 1.76 (1H, s), 1.94 (3H, s),
1.95-2.63 (7H, m), 3.18 (1H, d, J = 4.8Hz), 3.96 (1H, dd, J = 8.3Hz, J = 5.8Hz),
4.32 (1H, d, J = 8.3Hz), 4.37 (1H, d, J = 8.3Hz), 4.58 (1H, br d, J = 7.8Hz),
4.70-4.81 (2H, m), 5.10 (1H, d, J = 5.9Hz), 5.33 (1H, d, J = 8.4Hz),
5.46 (1H, d, J = 10.2Hz), 5.57 (1H, d, J = 17.6Hz), 5.90 (1H, d, J = 4.8Hz),
6.16 (1H, ddd, J = 17.6Hz, J = 10.2Hz, J = 5.9Hz), 7.47 (2H, t, J = 7.8Hz),
7.59 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).
[0521]
Reference Example 8
[0522]
Embedded image
Step 1: 9 β-4,10-dideacetyl-9-dihydro-4-O-propanoyl-9,10-O- (2-propenylidene) baccatin III
The compound obtained in Step 1 of Reference Example 7 was used as a raw material, and methyl iodide was used instead of ethyl iodide, and the same reaction operation as in Step 2 of Reference Example 7 was performed. Next, the same reaction operation as in step 3 of Reference Example 7 was performed to obtain the title compound as a white glass.
[0524]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.16 (3H, s), 1.26 (3H, t, J = 7.4Hz), 1.62 (3H, s), 1.65 (3H, s),
1.82 (1H, br s), 1.93 (3H, s), 2.09-2.25 (3H, m),
2.33 (1H, dd, J = 14.0Hz, J = 10.0Hz), 2.66 (2H, q, J = 7.4Hz),
3.05 (1H, d, J = 4.9Hz), 3.89 (1H, d, J = 7.4Hz), 4.06-4.16 (1H, br),
4.33 (1H, d, J = 8.8Hz), 4.39 (1H, d, J = 8.8Hz), 4.53-4.63 (1H, br),
4.72-4.84 (1H, br), 5.02 (1H, s like), 5.22 (1H, d, J = 6.4Hz),
5.30 (1H, d, J = 7.4Hz), 5.45 (1H, d, J = 10.8Hz), 5.56 (1H, d, J = 17.6Hz),
5.96-6.10 (2H, m), 7.47 (2H, t, J = 7.4Hz), 7.60 (1H, t, J = 7.4Hz),
8.13 (2H, d, J = 7.4Hz).
[0525]
Step 2: 9 β-4,10-dideacetyl-9-dihydro-4-O-propanoyl-9,10-O- (2-propenylidene) -7-O-triethylsilylbaccatin III
Using the compound obtained in Step 1 above as a raw material, the same reaction operation as in Step 1 of Reference Example 5 was performed to obtain a white glassy title compound.
[0526]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.58-0.71 (6H, m), 0.98 (9H, t, J = 7.8Hz), 1.09 (3H, s), 1.25 (3H, s),
1.56 (3H, s), 1.60 (3H, s), 1.75 (1H, s), 1.94 (3H, s), 1.98-2.16 (2H, m),
2.23-2.44 (2H, m), 2.62 (2H, q, J = 7.3Hz), 3.19 (1H, d, J = 5.4Hz),
3.96 (1H, dd, J = 8.8Hz, J = 5.8Hz), 4.32 (1H, d, J = 8.3Hz), 4.37 (1H, d, J = 8.3Hz),
4.59 (1H, d, J = 8.7Hz), 4.71-4.82 (2H, m), 5.09 (1H, d, J = 5.9Hz),
5.33 (1H, d, J = 8.7Hz), 5.46 (1H, d, J = 10.8Hz), 5.56 (1H, d, J = 17.6Hz),
5.90 (1H, d, J = 5.4Hz), 6.16 (1H, ddd, J = 17.6Hz, J = 10.8Hz, J = 5.9Hz),
7.46 (2H, t, J = 7.3Hz), 7.58 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz).
[0527]
Reference Example 9
[0528]
Embedded image
Step 1: 9 β-10-deacetyl-9-dihydro-9,10-O-isopropylidene-7,13-bis-O-triethylsilylbaccatin III
The title compound was obtained by carrying out the same reaction operation as in Step 1 of Reference Example 7 using the compound obtained in Step 1 of Reference Example 6 as a raw material.
[0530]
1H-NMR (400 MHz, CDCl3 / TMS) δ (ppm)
0.56-0.70 (12H, m), 0.90-1.04 (18H, m), 1.15 (3H, s), 1.31 (3H, s),
1.37 (3H, s), 1.45 (3H, s), 1.55 (3H, s), 1.87 (3H, s), 2.03-2.36 (4H, m),
2.27 (3H, s), 3.20 (1H, d, J = 5.8Hz), 3.94 (1H, dd, J = 9.2Hz, J = 3.6Hz),
4.42 (1H, d, J = 8.0Hz), 4.50 (1H, d, J = 8.0Hz), 4.54 (1H, d, J = 9.2Hz),
4.83 (1H, t, J = 7.3Hz), 4.94 (1H, dd, J = 8.2Hz, J = 7.8Hz), 5.41 (1H, d, J = 9.2Hz),
5.7 (1H, d, J = 5.8H), 7.44-7.84 (2H, m), 7.56-7.59 (1H, m), 8.07-8.09 (2H, m).
[0531]
Step 2: 9 β-4-O-butanoyl-4,10-dideacetyl-9-dihydro-9,10-O-isopropylidene-7,13-bis-O-triethylsilylbaccatin III
The title compound was obtained as a colorless glassy solid by carrying out the same reaction operation as in Step 2 of Reference Example 7 using the compound obtained in Step 1 as a raw material.
[0532]
1H-NMR (400 MHz, CDCl3 / TMS) δ (ppm)
0.58-0.70 (12H, m), 0.91-1.07 (21H, m), 1.16 (3H, s), 1.38 (3H, s),
1.46 (3H, s), 1.47 (3H, s), 1.56 (3H, s), 1.85 (3H, s), 2.04-2.28 (6H, m),
2.53 (1H, dt, J = 8.0Hz, J = 6.0Hz), 2.54 (1H, dt, J = 8.0Hz, J = 6.0Hz),
3.19 (1H, d, J = 5.9Hz), 3.97 (1H, dd, J = 9.9Hz, J = 3.9Hz),
4.37 (2H, AB type q, J = 7.8Hz), 4.54 (1H, d, J = 9.3Hz), 4.80 (1H, t, J = 7.3Hz),
4.94 (1H, t, J = 7.8Hz), 5.41 (1H, d, J = 9.3Hz), 5.79 (1H, d, J = 5.9Hz),
7.46 (2H, t, J = 7.8Hz), 7.57 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
FAB mass ： 843 (MH+)
[0533]
Step 3: 9 β-4-O-butanoyl-4,10-dideacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
The title compound was obtained as a colorless glassy solid by carrying out the same reaction operation as in step 3 of Reference Example 7 using the compound obtained in the above step 2 as a raw material.
[0534]
1H-NMR (400 MHz, CDCl3 / TMS) δ (ppm)
1.07 (3H, s), 1.16 (3H, s), 1.42 (3H, s), 1.58 (3H, s), 1.63 (3H, s),
1.64 (3H, s), 1.84 (3H, s), 1.93 (3H, s), 1.97-2.40 (4H, m),
2.59 (2H, dd, J = 7.8Hz, J = 7.3Hz), 3.06 (1H, d, J = 4.9Hz), 3.85 (1H, d, J = 7.3Hz),
4.10 (1H, s), 4.37 (2H, AB type q, J = 8.5Hz), 4.67 (1H, d, J = 7.8Hz),
4.79 (1H, dd, J = 8.5Hz, J = 5.7Hz), 5.02 (1H, br), 5.59 (1H, d, J = 7.3Hz),
6.03 (1H, d, J = 4.9Hz), 7.48 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.3Hz),
8.13 (2H, d, J = 7.3Hz).
[0535]
Step 4: 9 β-4-O-butanoyl-4,10-dideacetyl-9-dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
The title compound was obtained as a colorless glassy solid by carrying out the same reaction operation as in Step 1 of Reference Example 5 using the compound obtained in Step 3 above as a raw material.
[0536]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.61 (6H, q, J = 7.8Hz), 0.95 (9H, t, J = 7.8Hz), 1.06 (3H, t, J = 7.3Hz),
1.13 (3H, s), 1.41 (3H, s), 1.51 (3H, s), 1.57 (3H, s), 1.59 (3H, s),
1.77-1.83 (2H, m), 1.94 (3H, s), 2.27-2.39 (4H, m), 2.59 (2H, m),
3.65 (1H, d, J = 5.4Hz), 3.65 (1H, dd, J = 7.8Hz, J = 4.4Hz),
4.18 (2H, AB type q, J = 7.8Hz), 4.56 (1H, d, J = 7.8Hz), 4.48-4.83 (2H, m),
5.52 (1H, d, J = 7.8Hz), 5.93 (1H, d, J = 5.4Hz), 7.43 (2H, t, J = 7.8Hz),
7.59 (1H, t, J = 7.8Hz), 8.15 (2H, d, J = 7.8Hz).
[0537]
Reference Example 10
[0538]
Embedded image
Step 1: 9 β-4,10-dideacetyl-9-dihydro-9,10-O-isopropylidene-4-O-propanoyl-7,13-bis-O-triethylsilylbaccatin III
Under a nitrogen atmosphere, 1.17 ml of diisopropylamine was dissolved in 21 ml of dry tetrahydrofuran at 0 ° C., n-butyllithium (1.69 mol / L, hexane solution) was added, and the mixture was stirred for 20 minutes. This was cooled to −78 ° C., and 728 mg of the compound obtained in Step 1 of Reference Example 9 dissolved in 7 ml of dry tetrahydrofuran was added dropwise. After 1 hour, 1.11 ml of methyl iodide was added at −78 ° C., and the temperature was gradually raised to −5 ° C. while stirring for 4 hours. Saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 10: 1 (v / v)) to give the title compound as a colorless glassy solid.
mg was obtained.
[0540]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.61-0.72 (12H, m), 0.91-1.02 (18H, m), 1.16 (3H, s), 1.25 (3H, t, J = 7.3Hz),
1.38 (3H, s), 1.46 (3H, s), 1.50 (3H, s), 1.56 (3H, s), 1.85 (3H, s),
2.02-2.26 (4H, m), 2.63 (2H, q, J = 7.3Hz), 3.19 (1H, d, J = 5.9Hz),
3.96 (1H, dd, J = 9.3Hz, J = 3.4Hz), 4.30 (2H, AB type q, J = 7.8Hz),
4.54 (1H, d, J = 8.8Hz), 4.80 (1H, t, J = 7.3Hz), 4.95 (1H, t, J = 8.3Hz),
5.40 (1H, d, J = 9.3Hz), 5.78 (1H, d, J = 5.9Hz), 7.46 (2H, t, J = 7.3Hz),
7.58 (1H, t, J = 7.3Hz), 8.10 (2H, d, J = 7.3Hz).
FAB mass ： 829 (MH+)
[0541]
Step 2: 9 β-4,10-dideacetyl-9-dihydro-9,10-O-isopropylidene-4-O-propanoylbaccatin III
The title compound was obtained as a colorless glassy solid by carrying out the same reaction operation as in step 3 of Reference Example 7 using the compound obtained in the above step 1 as a raw material.
[0542]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.16 (3H, s), 1.27 (3H, t, J = 7.3Hz), 1.42 (3H, s), 1.50 (3H, s), 1.63 (3H, s),
1.64 (3H, s), 1.94 (3H, s), 2.11-2.36 (4H, m), 2.66 (2H, q, J = 7.3Hz),
3.06 (1H, d, J = 4.9Hz), 3.85 (1H, d, J = 7.3Hz), 4.52 (2H, AB type q, J = 8.3Hz),
4.67 (1H, d, J = 8.3Hz), 4.79 (1H, m), 5.02 (1H, s), 5.59 (1H, d, J = 7.3Hz),
6.02 (1H, d, J = 4.9Hz), 7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.14 (2H, d, J = 7.8Hz).
[0543]
Step 3: 9 β-4,10-dideacetyl-9-dihydro-9,10-O-isopropylidene-4-O-propanoyl-7-O-triethylsilylbaccatin III
The title compound was obtained as a colorless glassy solid by carrying out the same reaction operation as in Step 1 of Reference Example 5 using the compound obtained in Step 2 above as a raw material.
[0544]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.57-0.64 (6H, m), 0.93-0.98 (9H, m), 1.12 (3H, s), 1.26 (3H, t, J = 7.3Hz),
1.40 (3H, s), 1.51 (3H, s), 1.57 (3H, s), 1.58 (3H, s), 1.77 (1H, s),
1.94 (3H, s), 1.96-2.35 (4H, m), 2.65 (2H, q, J = 7.3Hz), 3.16 (1H, d, J = 5.6Hz),
4.08 (1H, t, J = 4.9Hz), 4.20 (2H, d, J = 7.8Hz), 4.56 (1H, d, J = 7.8Hz),
4.74-4.78 (2H, m), 5.20 (1H, d, J = 8.3Hz), 5.93 (1H, d, J = 5.4Hz),
7.46 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.15 (2H, d, J = 7.8Hz).
FAB mass ： 715 (MH+)
[0545]
Reference Example 11
[0546]
Embedded image
Step 1: 9 β-10-deacetyl-9-dihydro-1-O-dimethylsilyl-9,10-O- (2-propenylidene) -7,13-bis-O-triethylsilylbaccatin III
1.0789 g of the compound obtained in Step 1 of Reference Example 7 was dissolved in 26.9 ml of N, N-dimethylformamide, 0.595 g of imidazole was added at room temperature, and 0.736 ml of dimethylchlorosilane was added dropwise at 0 ° C. and stirred. After 1 hour, cold water was added at 0 ° C., and the mixture was extracted with a hexane-ethyl acetate mixed solvent (1: 1 (v / v)). The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 9: 1 (v / v)) to obtain 0.994 g of the title compound as a white foam. .
[0548]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.34 (3H, d, J = 2.9Hz), 0.03 (3H, d, J = 2.9Hz), 0.58-0.76 (12H, m),
0.92-1.09 (18H, m), 1.11 (3H, s), 1.522 (3H, s), 1.528 (3H, s), 1.86 (3H, s),
2.02-2.16 (1H, m), 2.23-2.44 (3H, m), 2.26 (3H, s), 3.19 (1H, d, J = 5.3Hz),
3.88 (1H, dd, J = 10.7Hz, J = 4.9Hz), 4.33 (1H, d, J = 7.8Hz),
4.41 (1H, d, J = 7.8Hz), 4.52-4.68 (2H, m), 4.83 (1H, dd, J = 8.8Hz, J = 5.4Hz),
4.98 (1H, t, J = 9.0Hz), 5.04 (1H, d, J = 6.4Hz), 5.27 (1H, d, J = 9.3Hz),
5.42 (1H, d, J = 10.7Hz), 5.53 (1H, d, J = 17.5Hz), 5.89 (1H, d, J = 5.3Hz),
6.11 (1H, ddd, J = 17.5Hz, J = 10.7Hz, J = 6.4Hz), 7.45 (2H, t, J = 7.8Hz),
7.56 (1H, t, J = 7.8Hz), 8.10 (2H, d, J = 7.8Hz).
[0549]
Step 2: 9 β-4,10-dideacetyl-9-dihydro-1-O-dimethylsilyl-9,10-O- (2-propenylidene) -7,13-bis-O-triethylsilylbaccatin III
0.994 g of the compound obtained in the above step 1 was dissolved in 50 ml of dry tetrahydrofuran, and 2.7 ml of sodium bis (2-methoxyethoxy) aluminum hydride (65% (w / v), toluene solution) was added dropwise at 0 ° C. The mixture was stirred at 0 ° C. for 50 minutes. At 0 ° C., 250 ml of diethyl ether was added, and an aqueous solution in which 12.8 g of potassium sodium tartrate tetrahydrate was dissolved in 70 ml of water was gradually added. After completion of the addition, the mixture was returned to room temperature and stirred vigorously for 1 hour. The mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 9: 1 (v / v)) to obtain 0.8413 g of the title compound as a colorless glass. .
[0550]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.27 (3H, d, J = 2.4Hz), -0.01 (3H, d, J = 2.4Hz), 0.54-0.67 (6H, m),
0.69-0.85 (6H, m), 0.95 (3H, t, J = 7.8Hz), 0.97 (3H, s), 1.05 (9H, t, J = 7.9Hz),
1.44 (3H, s), 1.55 (3H, s), 1.81 (3H, s),
2.10 (1H, ddd, J = 13.6Hz, J = 9.6Hz, J = 4.2Hz),
2.20 (1H, ddd, J = 13.6Hz, J = 8.2Hz, J = 6.0Hz), 2,52 (1H, dd, J = 14.7Hz, J = 9.8Hz),
2.87 (1H, d, J = 3.4Hz), 3.01 (1H, dd, J = 14.7Hz, J = 1.4Hz),
3.62 (1H, dd, J = 9.6Hz, J = 6.0Hz), 3.78 (1H, s like), 4.28 (1H, d, J = 7.9Hz),
4.38-4.50 (2H, m), 4.50-4.69 (2H, m), 5.07 (1H, d, J = 6.4Hz),
5.33 (1H, d, J = 7.9Hz), 5.44 (1H, d, J = 10.2Hz), 5.55 (1H, d, J = 17.1Hz),
5.97 (1H, d, J = 3.5Hz), 6.20 (1H, ddd, J = 17.1Hz, J = 10.2Hz, J = 6.4Hz),
7.43 (2H, t, J = 7.4Hz), 7.53 (1H, t, J = 7.4Hz), 8.15 (2H, d, J = 7.4Hz).
[0551]
Step 3: 9 β-4-O-cyclopropanecarbonyl-4,10-dideacetyl-9-dihydro-1-O-dimethylsilyl-9,10-O- (2-propenylidene) -7,13-bis-O -Triethylsilylbaccatin III
0.8413 g of the compound obtained in the above step 2 is dissolved in 40 ml of dry tetrahydrofuran, and 1.0 ml / L lithium bistrimethylsilylamide 3.1 ml (tetrahydrofuran solution) is added dropwise at 0 ° C. After 15 minutes, 0.24 ml of cyclopropanecarbonyl chloride is added. Added. After 45 minutes, saturated aqueous ammonium chloride solution was added at 0 ° C., and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 10: 1 (v / v) → hexane: ethyl acetate = 6: 1 (v / v)). Purification gave 0.8104 g of the title compound as a colorless glass.
[0552]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.33 (3H, d, J = 2.4Hz), 0.04 (3H, d, J = 2.4Hz), 0.57-0.75 (12H, m),
0.97 (9H, t, J = 7.8Hz), 1.02 (9H, t, J = 7.8Hz), 1.13 (3H, s), 1.20-1.46 (2H, m),
1.52 (3H, s), 1.56 (3H, s), 1.64-1.76 (1H, m), 1.87 (3H, s),
2.02 (1H, ddd, J = 14.4Hz, J = 10.4Hz, J = 4.4Hz), 2.22-2.41 (3H, m),
3.15 (1H, d, J = 5.4Hz), 3.88 (1H, dd, J = 10.4Hz, J = 5.4Hz),
4.25 (1H, d, J = 8.3Hz), 4.34 (1H, d, J = 8.3Hz), 4.52-4.64 (2H, m),
4.72 (1H, dd, J = 8.8Hz, J = 4.4Hz), 4.97 (1H, t, J = 8.3Hz), 5.05 (1H, d, J = 5.7Hz),
5.28 (1H, d, J = 8.8Hz), 5.42 (1H, d, J = 10.3Hz), 5.53 (1H, d, J = 17.6Hz),
5.91 (1H, d, J = 5.4Hz), 6.13 (1H, ddd, J = 17.6Hz, J = 10.3Hz, J = 5.7Hz),
7.45 (2H, t, J = 7.4Hz), 7.56 (1H, t, J = 7.4Hz), 8.08 (2H, d, J = 7.4Hz).
[0553]
Step 4: 9 β-4-O-cyclopropanecarbonyl-4,10-dideacetyl-9-dihydro-9,10-O- (2-propenylidene) baccatin III
Using the compound obtained in Step 3 above as a raw material, the same reaction operation as in Step 3 of Reference Example 7 was carried out to give the title compound as a colorless glass.
[0554]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.05-1.40 (4H, m), 1.17 (3H, s), 1.61 (3H, s), 1.73-2.48 (m), 1.92 (3H, s),
3.04 (1H, d, J = 4.4Hz), 3.86 (1H, d, J = 6.9Hz), 4.03-4.18 (1H, m),
4.36 (1H, d, J = 8.3Hz), 4.42 (1H, d, J = 8.3Hz), 4.57 (1H, d, J = 8.3Hz),
4.68-4.82 (1H, m), 4.98 (1H, s like), 5.22 (1H, d, J = 5.9Hz),
5.29 (1H, d, J = 6.9Hz), 5.45 (1H, d, J = 10.2Hz), 5.56 (1H, d, J = 17.1Hz),
5.94-6.11 (2H, m), 7.48 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz),
8.13 (2H, d, J = 7.8Hz).
[0555]
Step 5: 9 β-4-O-cyclopropanecarbonyl-4,10-dideacetyl-9-dihydro-9,10-O- (2-propenylidene) -7-O- triethylsilylbaccatin III
Using the compound obtained in Step 4 above as a raw material, the same reaction operation as in Step 1 of Reference Example 5 was carried out to give the title compound as a colorless glass.
[0556]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.58-0.72 (6H, m), 0.97 (9H, t, J = 7.8Hz), 1.06-1.39 (4H, m), 1.10 (3H, s),
1.56 (3H, s), 1.62 (3H, s), 1.74-1.88 (2H, m), 1.98 (3H, s),
1.98-2.21 (3H, m), 2.28-2.44 (2H, m), 3.16 (1H, d, J = 5.3Hz),
3.95 (1H, dd, J = 8.3Hz, J = 5.9Hz), 4.30 (1H, d, J = 8.3Hz), 4.38 (1H, d, J = 8.3Hz),
4.54 (1H, d, J = 7.8Hz), 4.68-4.82 (2H, m), 5.10 (1H, d, J = 5.8Hz),
5.33 (1H, d, J = 7.8Hz), 5.45 (1H, d, J = 10.3Hz), 5.56 (1H, d, J = 17.6Hz),
5.93 (1H, d, J = 5.3Hz), 6.16 (1H, ddd, J = 17.6Hz, J = 10.3Hz, J = 5.8Hz),
7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).
[0557]
Reference Example 12
[0558]
Embedded image
Step 1: 9 β-10-deacetyl-9-dihydro-1-O-dimethylsilyl-9,10-O-isopropylidene-7,13-bis-O-triethylsilylbaccatin III
The compound obtained in Step 1 of Reference Example 8 was used as a raw material, and the same reaction operation as in Step 1 of Reference Example 11 was performed to obtain a colorless glassy title compound.
[0560]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.33 (3H, d, J = 2.9Hz), 0.04 (3H, d, J = 2.9Hz), 0.58-0.72 (12H, m),
0.94-1.05 (18H, m), 1.12 (3H, s), 1.37 (3H, s), 1.47 (3H, s), 1.49 (3H, s),
1.57 (3H, s), 1.86 (3H, s), 2.09-2.36 (4H, m), 2.30 (3H, s),
3.19 (1H, d, J = 5.9Hz), 3.91 (1H, dd, J = 8.8Hz, J = 3.4Hz),
4.40 (2H, AB type q, J = 8.8Hz), 4.50 (1H, d, J = 8.8Hz), 4.57 (1H, m),
4.83 (1H, t, J = 7.3Hz), 4.97 (1H, t, J = 8.3Hz), 5.40 (1H, d, J = 8.8Hz),
5.84 (1H, d, J = 5.4Hz), 7.46 (2H, t, J = 7.8Hz), 7.57 (1H, t, J = 7.8Hz),
8.09 (2H, d, J = 7.8Hz).
[0561]
Step 2: 9 β-4,10-dideacetyl-9-dihydro-1-O-dimethylsilyl-9,10-O-isopropylidene-7,13-bis-O-triethylsilylbaccatin III
Using the compound obtained in Step 1 above as a raw material, the same reaction operation as in Step 2 of Reference Example 11 was carried out to obtain a colorless glassy title compound.
[0562]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.27 (3H, d, J = 2.9Hz), 0.01 (3H, d, J = 2.9Hz), 0.58-0.83 (12H, m),
0.93-1.10 (18H, m), 1.08 (3H, s), 1.39 (3H, s), 1.46 (3H, s), 1.55 (3H, s),
1.77 (3H, s), 1.84-2.40 (4H, m), 2.51 (1H, dd, J = 15.1Hz, J = 10.0Hz),
2.73 (1H, d, J = 5.9Hz), 3.03 (1H, dd, J = 15.1Hz, J = 2.4Hz), 3.64 (1H, s),
3.86 (1H, dd, J = 7.3Hz, J = 2.9Hz), 4.05 (1H, d, J = 7.8Hz), 4.09 (1H, d, J = 6,8Hz),
4.43 (1H, m), 4.52 (1H, d, J = 6.8Hz), 4.62-4.65 (2H, m), 5.54 (1H, d, J = 7.3Hz),
5.57 (1H, t, J = 3.9Hz), 7.44 (2H, t, J = 7.8Hz), 7.55 (1H, t, J = 7.8Hz),
8.19 (2H, d, J = 7.8Hz).
[0563]
Step 3: 9 β-4-O-cyclopropanecarbonyl-4,10-dideacetyl-9-dihydro-1-O-dimethylsilyl-9,10-O-isopropylidene-7,13-bis-O-triethylsilyl Baccatin III
Using the compound obtained in Step 2 above as a raw material, the same reaction operation as in Step 3 of Reference Example 11 was performed to obtain a colorless glassy title compound.
[0564]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.32 (3H, d, J = 2.4Hz), 0.05 (3H, d, J = 2.4Hz), 0.58-0.71 (12H, m),
0.94-1.04 (18H, m), 1.16 (3H, s), 1.21-1.36 (4H, m), 1.38 (3H, s),
1.48 (3H, s), 1.53 (3H, s), 1.55 (3H, s), 1.71 (1H, m), 1.87 (3H, s),
2.05-2.38 (4H, m), 3.13 (1H, d, J = 5.4Hz), 3.87 (1H, dd, J = 8.8Hz, J = 3.4Hz),
4.20 (2H, AB type q, J = 7.8Hz), 4.41 (1H, d, J = 8.8Hz), 4.60 (1H, m),
4.43 (1H, t, J = 6.3Hz), 4.99 (1H, t, J = 8.3Hz), 5.42 (1H, d, J = 8.8Hz),
5.88 (1H, d, J = 5.4Hz), 7.46 (2H, t, J = 7.8Hz), 7.57 (1H, t, J = 7.8Hz),
8.10 (2H, d, J = 7.8Hz).
FAB mass ： 899 (MH+)
[0565]
Step 4: 9 β-4-O-cyclopropanecarbonyl-4,10-dideacetyl-9-dihydro-9,10-O-isopropylidenebaccatin III
Using the compound obtained in Step 3 above as a raw material, the same reaction operation as in Step 3 of Reference Example 7 was carried out to give the title compound as a colorless glass.
[0566]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.15-1.37 (7H, m), 1.41 (3H, s), 1.58 (3H, s), 1.64 (6H, s), 1.82-2.41 (5H, m),
1.73 (3H, s), 3.05 (1H, d, J = 4.9Hz), 3.82 (1H, d, J = 6.8Hz), 4.08 (1H, br),
4.39 (2H, AB type q, J = 8.3Hz), 4.67 (1H, br), 4.76 (1H, t, J = 7.2Hz),
4.99 (1H, s), 5.59 (1H, d, J = 6.8Hz), 6.06 (1H, d, J = 4.9Hz),
7.48 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz), 8.13 (2H, d, J = 7.3Hz).
FAB mass ： 813 (MH+)
[0567]
Step 5: 9 β-4-O-cyclopropanecarbonyl-4,10-dideacetyl-9-dihydro-9,10-O-isopropylidene-7-O-triethylsilylbaccatin III
Using the compound obtained in Step 4 above as a raw material, the same reaction operation as in Step 1 of Reference Example 5 was carried out to give the title compound as a colorless glass.
[0568]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.58-0.64 (6H, m), 0.71-0.88 (9H, m), 1.05-1.22 (4H, m), 1.14 (3H, s),
1.41 (3H, s), 1.57 (3H, s), 1.60 (3H, s), 1.86-2.08 (5H, m), 1.93 (3H, s),
3.11 (1H, d, J = 4.9Hz), 4.09-4.27 (2H, m), 4.50 (2H, AB type q, J = 7.8Hz),
4.71-4.80 (2H, m), 5.53 (1H, d, J = 7.8Hz), 5.96 (1H, d, J = 4.8Hz),
7.48 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.15 (2H, d, J = 7.3Hz).
[0569]
Reference Example 13
[0570]
Embedded image
Step 1: 9 β-10-deacetyl-7-deoxy-6,7-didehydro-9-dihydro-9,10-O-isopropylidene-13-O-triethylsilylbaccatin III
470 mg of the compound obtained in Step 3 of Example 10 was dissolved in 45 ml of methylene chloride, and 15 ml of pyridine and 570 μl of trifluoromethanesulfonic anhydride were added at 0 ° C. After stirring at room temperature for 1 hour, the reaction mixture was poured into 100 ml of stirred diethyl ether and 50 ml of saturated aqueous sodium bicarbonate, extracted with diethyl ether, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (v / v), changed to 2: 1 (v / v) halfway) Then, 240 mg of the title compound was obtained as a white solid, and 107 mg of the raw material was recovered.
[0572]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.57-0.74 (6H, m), 1.01 (9H, t, J = 8.9Hz), 1.20 (3H, s), 1.40 (3H, s),
1.51 (3H, s), 1.54 (3H, s), 1.57 (3H, s), 1.75 (1H, s), 1.84 (3H, s),
2.13 (1H, dd, J = 8.1, J = 14.7Hz), 2.22 (1H, dd, J = 8.6, J = 14.7Hz), 2.29 (3H, s),
3.09 (1H, d, J = 6.2Hz), 4.14 (1H, d, J = 8.1Hz), 4.27-4.33 (2H, m),
4.90 (1H, d, J = 4.3Hz), 4.97 (1H, br t, J = 8.8Hz), 5.48 (1H, d, J = 8.1Hz),
5.66 (1H, dd, J = 10.3, J = 4.3Hz), 5.87 (1H, d, J = 6.2Hz), 6.08 (1H, d, J = 10.3Hz),
7.49 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.8Hz), 8.15 (2H, d, J = 7.8Hz).
[0573]
Step 2: 9 β-10-deacetyl-7-deoxy-6,7-didehydro-9-dihydro-9,10-O-isopropylidenebaccatin III
The title compound was obtained as a white solid by carrying out the same reaction operation as in step 4 of Example 1 using the compound obtained in the above step 1.
[0574]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.13 (3H, s), 1.42 (3H, s), 1.53 (3H, s), 1.54 (3H, s), 1.59 (3H, s),
1.75 (1H, s), 1.91 (3H, s), 2.09 (1H, dd, J = 6.8, J = 15.2Hz),
2.20 (1H, br d, J = 7.8Hz), 2.34 (1H, dd, J = 8.8, J = 15.2Hz), 2.35 (3H, s),
3.22 (1H, d, J = 5.9Hz), 4.04 (1H, d, J = 7.4Hz), 4.26 (1H, d, J = 8.1Hz),
4.34 (1H, d, J = 8.1Hz), 4.72-4.87 (1H, m), 4.83 (1H, d, J = 4.4Hz),
5.54 (1H, d, J = 7.4Hz), 5.66 (1H, dd, J = 10.3, J = 4.4Hz), 5.93 (1H, d, J = 5.9Hz),
6.12 (1H, d, J = 10.3Hz), 7.48 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz),
8.18 (2H, d, J = 7.3Hz).
[0575]
Reference Example 14
[0576]
Embedded image
Step 1: 9 β-10-deacetyl-7-deoxy-9-dihydro-7α-fluorobaccatin III
26.1 mg of 10-deacetyl-7-deoxy-7α-fluorobaccatin III was dissolved in 1.5 ml of tetrahydrofuran, and 1.5 ml of borane-tetrahydrofuran (1.0 M tetrahydrofuran solution) was added at 0 ° C. After stirring at 0 ° C. for 6 hours, methanol (3.0 ml) was added dropwise, and the mixture was stirred at room temperature for 30 minutes. The solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel thin layer chromatography (developing solvent; chloroform: acetone = 3: 1 (v / v)) to obtain 30.8 mg of the title compound as a colorless transparent glassy substance.
[0578]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.14 (3H, s), 1.63 (3H, s), 1.71 (3H, s), 1.77 (1H, s), 1.87-1.90 (3H, m),
2.11 (1H, dd, J = 5.9, J = 15.6Hz), 2.15-2.52 (4H, m), 2.32 (3H, s), 3.34 (1H, s),
3.56 (1H, d, J = 4.9Hz), 4.06 (1H, d, J = 5.4Hz), 4.22 (1H, d, J = 8.3Hz),
4.42 (1H, d, J = 8.3Hz), 4.71 (1H, dd, J = 5.4, J = 48.3Hz), 4.72-4.83 (1H, m),
4.99 (1H, d, J = 7.8Hz), 5.27 (1H, br s), 6.08 (1H, d, J = 4.9Hz),
7.48 (2H, t, J = 7.8Hz), 7.59 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).
[0579]
Step 2: 9 β-10-deacetyl-7-deoxy-9-dihydro-7α-fluoro-9,10-O-isopropylidenebaccatin III
The title compound was obtained as a colorless and transparent glassy substance by carrying out the same reaction operation as in Step 2 of Example 1 using the compound obtained in Step 1 above.
[0580]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.12 (3H, s), 1.43 (3H, s), 1.49 (3H, s), 1.59 (3H, s), 1.65 (3H, s),
1.75 (1H, s), 1.98 (3H, d, J = 1.5Hz), 2.00-2.45 (5H, m), 2.33 (3H, s),
3.59 (1H, d, J = 5.2Hz), 4.30 (1H, d, J = 8.8Hz), 4.35 (1H, d, J = 8.8Hz),
4.61 (1H, d, J = 8.8Hz), 4.75-4.85 (1H, m),
4.92 (1H, ddd, J = 3.4, J = 10.3, J = 45.9Hz), 4.94 (1H, d, J = 3.9Hz),
5.59 (1H, d, J = 8.8Hz), 5.89 (1H, d, J = 5.2Hz), 7.48 (2H, t, J = 7.4Hz),
7.61 (1H, t, J = 7.4Hz), 8.12 (2H, d, J = 7.4Hz).
[0581]
Reference Example 15
[0582]
Embedded image
Step 1: 10,13-Di-O-benzyloxycarbonyl-10-deacetyl-7-O- trifluoromethanesulfonylbaccatin III
Dissolve 470 mg of 10,13-di-O-benzyloxycarbonyl-10-deacetylbaccatin III in 20 ml of methylene chloride, add 700 mg of 4-dimethylaminopyridine and 480 μl of trifluoromethanesulfonic anhydride at 0 ° C. did. After stirring at 0 ° C. for 1 hour, the reaction mixture was poured into 50 ml of stirred ethyl acetate and 50 ml of ice water, extracted with ethyl acetate, washed with saturated aqueous sodium bicarbonate, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; chloroform: ethyl acetate = 1: 1 (v / v)) to obtain 370 mg of the title compound as a white solid.
[0584]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.10 (3H, s), 1.18 (3H, s), 1.68 (1H, s), 1.86 (3H, s), 2.13 (3H, d, J = 1.5Hz),
2.18-2.45 (3H, m), 2.28 (3H, s), 2.78-2.93 (1H, m), 3.94 (1H, d, J = 6.8Hz),
4.13 (1H, d, J = 8.3Hz), 4.33 (1H, d, J = 8.3Hz), 4.91 (1H, d, J = 8.3Hz),
5.20 (1H, d, J = 12.2Hz), 5.24 (2H, s), 5.25 (1H, d, J = 12.2Hz),
5.50 (1H, dd, J = 7.3, J = 10.3Hz), 5.67 (1H, d, J = 6.8Hz), 5.92 (1H, t, J = 8.1Hz),
6.48 (1H, s), 7.27-7.39 (10H, m), 7.48 (2H, t, J = 7.3Hz),
7.62 (1H, t, J = 7.3Hz), 8.05 (2H, d, J = 7.3Hz).
[0585]
Step 2: 10,13-di-O-benzyloxycarbonyl-10-deacetyl-7-deoxy-7β, 8β-methylene-19-norbaccatin III
Dissolve 220 mg of the compound obtained in the above Step 1 in 12 ml of tetrahydrofuran and 12 ml of acetonitrile, add 6.0 g of silica gel, stir at 60 ° C. for 24 hours, remove the silica gel by filtration, 50 ml of ethyl acetate and saturated aqueous sodium bicarbonate 50 ml was added, extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 3: 1 (v / v)) to obtain 170 mg of the title compound as a white solid.
[0586]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.14 (3H, s), 1.22 (3H, s), 1.39 (1H, br s), 1.58 (1H, s), 1.60-1.70 (1H, m),
1.94 (3H, d, J = 1.0Hz), 2.09 (1H, d, J = 16.1Hz), 2.23-2.40 (3H, m),
2.23 (3H, s), 2.45 (1H, dt, J = 16.1,4.4Hz), 4.01 (1H, d, J = 7.3Hz),
4.10 (1H, d, J = 8.8Hz), 4.29 (1H, d, J = 8.8Hz), 4.72 (1H, d, J = 3.9Hz),
5.17-5.30 (4H, m), 5.63 (1H, d, J = 7.3Hz), 5.80-5.92 (1H, m), 6.12 (1H, s),
7.28-7.50 (10H, m), 7.48 (2H, t, J = 7.3Hz), 7.61 (1H, t, J = 7.3Hz),
8.08 (2H, d, J = 7.3Hz).
[0587]
Step 3: 10-deacetyl-7-deoxy-7β, 8β-methylene-19-norbaccatin III
170 mg of the compound obtained in the above step 2 was dissolved in 10 ml of ethanol, 10% -palladium-carbon 34.0 ml was added at room temperature, stirred for 1 hour in a hydrogen atmosphere, filtered, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent; hexane: ethyl acetate = 1: 1 (v / v)) to obtain 110 mg of the title compound as a white solid.
[0588]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.11 (3H, s), 1.15 (3H, s), 1.35-1.43 (1H, m), 1.74 (1H, dd, J = 5.2,7.1Hz),
1.76 (1H, s), 2.03 (3H, d, J = 1.0Hz), 2.07-2.15 (2H, m), 2.27 (3H, s),
2.20-2.40 (2H, m), 2.45 (1H, dt, J = 15.6,4.4Hz), 4.06 (1H, d, J = 7.8Hz),
4.22 (1H, d, J = 1.0Hz), 4.23 (1H, d, J = 8.3Hz), 4.32 (1H, d, J = 8.3Hz),
4.75 (1H, d, J = 3.9Hz), 4.82-4.90 (1H, m), 5.04 (1H, s), 5.62 (1H, d, J = 7.8Hz),
7.49 (2H, t, J = 7.3Hz), 7.61 (1H, t, J = 7.3Hz), 8.13 (2H, d, J = 7.3Hz).
[0589]
Step 4: 9 β-10-deacetyl-7-deoxy-9-dihydro-7β, 8β-methylene-19-norbaccatin III
The title compound was obtained as a colorless and transparent glassy material by carrying out the same reaction operation as in Step 1 of Reference Example 14 using the compound obtained in Step 3 above.
[0590]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.92 (1H, br s), 1.06-1.18 (1H, m), 1.14 (3H, s), 1.39-1.48 (2H, m),
1.67 (3H, s), 1.78 (1H, s), 1.83 (3H, s), 2.16 (1H, d, J = 4.9Hz), 2.19 (3H, s),
2.34-2.40 (1H, m), 2.43 (1H, dd, J = 9.3,15.9Hz), 2.53 (1H, dd, J = 7.1,15.9Hz),
2.61 (1H, d, J = 7.8Hz), 2.58-2.68 (1H, m), 3.25 (1H, d, J = 7.8Hz),
3.87 (1H, dd, J = 5.4,7.8Hz), 4.18 (1H, d, J = 7.3Hz),
4.58 (1H, dd, J = 7.8,10.7Hz), 4.69 (1H, d, J = 7.3Hz), 4.70-4.80 (1H, m),
5.27 (1H, dd, J = 4.4,5.4Hz), 5.55 (1H, d, J = 7.8Hz), 7.47 (2H, t, J = 7.3Hz),
7.58 (1H, t, J = 7.3Hz), 8.04 (2H, d, J = 7.3Hz).
[0591]
Step 5: 9 β-10-deacetyl-7-deoxy-9-dihydro-7β, 8β-methylene-9,10-O-isopropylidene-19-norbaccatin III
The title compound was obtained as a colorless and transparent glassy substance by carrying out the same reaction operation as in Step 2 of Example 1 using the compound obtained in Step 4 above.
[0592]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.11 (3H, s), 1.20-1.40 (2H, m), 1.34 (3H, s), 1.48 (3H, s), 1,53 (3H, s),
1.68-1.80 (2H, m), 1.70 (1H, s), 1.76 (1H, t, J = 5.3Hz), 1.92 (3H, d, J = 1.0Hz),
2.09 (1H, d, J = 5.4Hz), 2.22 (3H, s), 2.37 (1H, dd, J = 8.3,15.6Hz),
2.47 (1H, dd, J = 7.3,15.6Hz), 2.70 (1H, dt, J = 14.7,8.3Hz),
3.31 (1H, d, J = 8.3Hz), 4.22 (1H, d, J = 7.8Hz), 4.40 (1H, d, J = 7.8Hz),
4.49 (1H, d, J = 7.8Hz), 4.57 (1H, dd, J = 8.2,9.2Hz), 4.75-4.85 (1H, m),
5.49 (1H, d, J = 7.8Hz), 5.50 (1H, d, J = 8.3Hz), 7.43 (2H, t, J = 7.3Hz),
7.59 (1H, t, J = 7.3Hz), 8.05 (2H, d, J = 7.3Hz).
[0593]
Reference Example 16
[0594]
Embedded image
Process 1: 10-deacetyl-10-O-formylbaccatin III
104 mg of 10-deacetylbaccatin III was dissolved in 1.0 ml of N, N-dimethylformamide, and 70.7 mg of 4-dimethylaminopyridine and 96.0 μl of trifluoromethanesulfonic anhydride were added at 0 ° C. After stirring at 0 ° C. for 10 minutes, the reaction mixture was poured into 10 ml of stirred ethyl acetate and 40 ml of water, extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: ethyl acetate = 1: 2 (v / v)) to obtain 94.3 mg of the title compound as a white solid. .
[0596]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.11 (3H, s), 1.12 (3H, s), 1.60 (3H, s), 1.69 (3H, s), 1.80-2.40 (5H, m),
2.29 (3H, s), 2.53-2.62 (1H, m), 3.89 (1H, d, J = 6.8Hz), 4.16 (1H, d, J = 8.7Hz),
4.31 (1H, d, J = 8.7Hz), 4.40-4.50 (1H, m), 4.90 (1H, br q, J = 5.6Hz),
4.98 (1H, d, J = 7.9Hz), 5.64 (1H, d, J = 6.8Hz), 6.46 (1H, s),
7.50 (2H, t, J = 7.2Hz), 7.61 (1H, t, J = 7.2Hz), 8.10 (2H, d, J = 7.2Hz),
8.22 (1H, s)
[0597]
Step 2: 10-deacetyl-10-O-formyl-7-O-[(1-imidazolyl) thiocarbonyl] baccatin III
23.8 mg of the compound obtained in the above Step 1 was dissolved in 0.50 ml of tetrahydrofuran, and 0.50 ml of benzene, 12.5 μl of 1,8-diazabicycloundecene and 12.5 mg of thiocarbonylimidazole were added at room temperature. After stirring at room temperature for 1 hour, 10 ml of ethyl acetate and 10 ml of saturated aqueous ammonium chloride solution were added to the reaction solution, extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; chloroform: ethyl acetate = 1: 1 (v / v)) to obtain 21.4 mg of the title compound as a white solid. .
[0598]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.13 (3H, s), 1.18 (3H, s), 1.64 (3H, s), 1.85-2.45 (4H, m), 1.96 (3H, s),
2.34 (3H, s), 2.49 (1H, br s), 3.04 (1H, ddd, J = 7.1, J = 9.3, J = 14.3Hz),
4.12 (1H, d, J = 7.3Hz), 4.21 (1H, d, J = 8.6Hz), 4.38 (1H, d, J = 8.6Hz),
4.88 (1H, br s), 5.04 (1H, d, J = 9.3Hz), 5.69 (1H, d, J = 7.3Hz),
6.26 (1H, dd, J = 7.1, J = 10.5Hz), 6.40 (1H, s), 7.00 (1H, s),
7.50 (2H, t, J = 7.2Hz), 7.52 (1H, s), 7.63 (1H, t, J = 7.2Hz), 7.99 (1H, s),
8.12 (2H, d, J = 7.2Hz), 8.18 (1H, s)
[0599]
Step 3: 10-deacetyl-7-deoxy-10-O-formylbaccatin III
140 mg of the compound obtained in the above Step 2 was dissolved in 5.0 ml of dioxane, and 280 μl of tributyltin hydride and 10.0 mg of 2,2′-azobisisobutyronitrile were added at room temperature. After stirring at 75-80 ° C. for 40 minutes, 10 ml of ethyl acetate, 10 ml of water and 10 ml of saturated brine were added to the reaction solution, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 5: 7 (v / v)) to obtain 52.0 mg of the title compound as a white solid.
[0600]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.09 (3H, s), 1.12 (3H, s), 1.50-2.50 (8H, m), 1.75 (3H, s), 2.04 (3H, s),
2.29 (3H, s), 3.85 (1H, d, J = 7.3Hz), 4.19 (1H, d, J = 8.3Hz),
4.32 (1H, d, J = 8.3Hz), 4.85 (1H, br s), 4.97 (1H, dd, J = 9.3, J = 2.5Hz),
5.63 (1H, d, J = 7.3Hz), 6.60 (1H, s), 7.49 (2H, t, J = 7.3Hz),
7.63 (1H, t, J = 7.3Hz), 8.12 (2H, d, J = 7.3Hz), 8.24 (1H, s)
[0601]
Process 4: 10-deacetyl-7-deoxybaccatin III
50.0 mg of the compound obtained in the above step 3 is dissolved in 2.0 ml of 95% ethanol, 200 μl of hydrazine hydrate is added at room temperature and stirred for 30 minutes, and then 10 ml of ethyl acetate and 50 ml of 7% hydrochloric acid are added to the reaction solution. The mixture was extracted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 2: 3 (v / v)) to obtain 30.0 mg of the title compound as a white solid. .
[0602]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.06 (3H, s), 1.09 (3H, s), 1.50-1.55 (1H, m), 1.80 (1H, s),
1.90-2.41 (7H, m), 2.17 (3H, s), 2.29 (3H, s), 3.92 (1H, d, J = 7.3Hz),
4.17 (1H, d, J = 1.5Hz), 4.22 (1H, d, J = 8.3Hz), 4.33 (1H, d, J = 8.3Hz),
4.82-4.92 (1H, m), 4.96 (1H, dd, J = 9.6, J = 3.2Hz), 5.24 (1H, d, J = 1.5Hz),
5.62 (1H, d, J = 7.3Hz), 7.48 (2H, t, J = 7.3Hz), 7.61 (1H, t, J = 7.3Hz),
8.12 (2H, d, J = 7.3Hz)
[0603]
Step 5: 9 β-10-deacetyl-7-deoxy-9-dihydrobaccatin III
The title compound was obtained as a colorless and transparent glassy substance by carrying out the same reaction operation as in Step 1 of Reference Example 14 using the compound obtained in Step 4 above.
[0604]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.15 (3H, s), 1.51 (3H, s), 1.67 (3H, s), 1.91 (3H, s), 1.50-2.70 (9H, m),
2.35 (3H, s), 3.04 (1H, d, J = 4.9Hz), 3.14 (1H, br d, J = 6.8Hz),
3.75 (1H, br s), 4.21 (1H, d, J = 8.3Hz), 4.37 (1H, d, J = 8.3Hz),
4.71 (1H, br q, J = 8.3Hz), 4.86 (1H, br s), 5.45 (1H, br s),
6.05 (1H, d, J = 4.9Hz), 7.48 (2H, t, J = 7.6Hz), 7.61 (1H, t, J = 7.6Hz),
8.14 (2H, d, J = 7.6Hz).
[0605]
Step 6: 9 β-10-deacetyl-7-deoxy-9-dihydro-9,10-O-isopropylidenebaccatin III
The title compound was obtained as a colorless transparent glassy substance by carrying out the same reaction operation as in step 2 of Example 1 using the compound obtained in the above step 5.
[0606]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.16 (3H, s), 1.43 (3H, s), 1.51 (3H, s), 1.57 (3H, s), 1.59 (3H, s),
1.79 (1H, s), 1.99 (3H, s), 1.45-2.40 (6H, m), 2.35 (3H, s),
2.44 (1H, d, J = 5.3Hz), 3.10 (1H, d, J = 4.9Hz), 4.19 (1H, d, J = 7.6Hz),
4.27 (1H, d, J = 8.3Hz), 4.34 (1H, d, J = 8.3Hz), 4.70-4.84 (1H, m),
4.86 (1H, br s), 5.62 (1H, d, J = 7.6Hz), 5.97 (1H, d, J = 4.9Hz),
7.48 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz), 8.14 (2H, d, J = 7.3Hz).
[0607]
Reference Example 17
[0608]
Embedded image
Step 1: 9 β-10-deacetyl-7-deoxy-9-dihydro-9,10-O- (2-propenylidene) baccatin III
0.4800 g of the compound obtained in Step 5 of Reference Example 16 was dissolved in 9.6 ml of methylene chloride, and 0.69 ml of acrolein diethyl acetal and 19 mg of camphorsulfonic acid were added at room temperature. After 20 minutes, the mixture was cooled to 0 ° C., and triethylamine was added to adjust to pH 8. This was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent; chloroform: acetone = 12: 1 (v / v)) to obtain 0.1823 g of the title compound as a white glassy solid.
[0610]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.15 (3H, s), 1.48 (3H, s), 1.59 (3H, s), 1.72-2.22 (4H, m), 1.96 (3H, s),
2.22-2.40 (1H, m), 2.33 (3H, s), 2.55 (1H, br d, J = 8.8Hz),
3.06 (1H, d, J = 5.4Hz), 4.19 (1H, d, J = 6.9Hz), 4.23 (1H, d, J = 8.3Hz),
4.32 (1H, d, J = 8.3Hz), 4.77 (1H, br), 4.84 (1H, s), 5.23 (1H, d, J = 6.4Hz),
5.32 (1H, d, J = 6.9Hz), 5.44 (1H, d, J = 10.2Hz), 5.57 (1H, d, J = 15.2Hz),
5.92-6.13 (2H, m), 7.46 (2H, t, J = 7.8Hz), 7.57 (1H, t, J = 7.8Hz),
8.13 (2H, d, J = 7.8Hz).
[0611]
Step 2: 9 β-10-deacetyl-7-deoxy-9-dihydro-9,10-O- (2-propenylidene) -13-O-triethylsilylbaccatin III
Using the compound obtained in Step 1 above as a raw material, the same reaction operation as in Step 1 of Reference Example 7 was performed to obtain the title compound as a white glassy solid.
[0612]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
0.58-0.76 (6H, m), 1.01 (9H, s), 1.25 (3H, s), 1.49 (3H, s), 1.61 (3H, s),
1.82-2.18 (6H, m), 1.93 (3H, s), 2.25 (3H, s), 2.92 (1H, d, J = 4.9Hz),
4.14 (1H, d, J = 8.3Hz), 4.24 (1H, d, J = 7.3Hz), 4.34 (1H, d, J = 8.3Hz),
4.93-5.05 (2H, m), 5.20 (1H, d, J = 6.4Hz), 5.28 (1H, d, J = 7.3Hz),
5.44 (1H, d, J = 10.7Hz), 5.56 (1H, d, J = 17.1Hz), 5.91-6.09 (2H, m),
7.47 (2H, t, J = 7.8Hz), 7.58 (1H, t, J = 7.8Hz), 8.14 (2H, d, J = 7.8Hz).
[0613]
Step 3: 9 β-10-deacetyl-7-deoxy-9-dihydro-1-O-dimethylsilyl-9,10-O- (2-propenylidene) -13-O-triethylsilylbaccatin III
Using the compound obtained in Step 2 above as a raw material, the same reaction operation as in Step 1 of Reference Example 11 was performed to obtain the title compound as a colorless and transparent oil.
[0614]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.28 (3H, d, J = 2.9Hz), 0.05 (3H, d, J = 2.9Hz), 0.59-0.78 (6H, m),
1.02 (9H, t, J = 7.8Hz), 1.19 (3H, s), 1.50-1.64 (1H, m), 1.53 (3H, s),
1.59 (3H, s), 1.82-2.04 (3H, m), 1.89 (3H, s),
2.14 (1H, dd, J = 15.1Hz, J = 8.3Hz), 2.26 (3H, s),
2.33 (1H, dd, J = 15.1Hz, J = 8.8Hz), 2.88 (1H, d, J = 4.8Hz),
4.17 (1H, d, J = 8.3Hz), 4.23 (1H, d, J = 7.3Hz), 4.30 (1H, d, J = 8.3Hz),
4.54-4.62 (1H, m), 4.94 (1H, s), 4.99 (1H, t, J = 8.3Hz), 5.19 (1H, d, J = 6.3Hz),
5.27 (1H, d, J = 7.3Hz), 5.42 (1H, d, J = 10.7Hz), 5.55 (1H, d, J = 17.1Hz),
5.92-6.06 (2H, m), 7.45 (2H, t, J = 7.9Hz), 7.56 (1H, t, J = 7.9Hz),
8.14 (2H, d, J = 7.9Hz).
[0615]
Step 4: 9 β-4,10-dideacetyl-7-deoxy-9-dihydro-1-O-dimethylsilyl-9,10-O- (2-propenylidene) -13-O-triethylsilylbaccatin III
Using the compound obtained in Step 3 above as a raw material, the same reaction operation as in Step 2 of Reference Example 11 was performed to obtain the title compound as a pale yellow transparent oil.
[0616]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.26 (3H, d, J = 2.9Hz), 0.01 (3H, d, J = 2.9Hz), 0.68-0.87 (6H, m),
1.03 (3H, s), 1.05 (9H, t, J = 7.8Hz), 1.42 (3H, s), 1.52 (3H, s),
1.52-1.73 (2H, m), 1.80 (3H, s), 1.80-1.95 (2H, m),
2.52 (1H, dd, J = 15.1Hz, J = 9.7Hz), 2.71 (1H, d, J = 4.4Hz),
2.85 (1H, dd, J = 15.1Hz, J = 2.4Hz), 3.61 (1H, s), 4.12-4.31 (1H, m),
4.14 (1H, d, J = 7.3Hz), 4.18 (1H, d, J = 7.3Hz), 4.25 (1H, d, J = 7.3Hz),
4.57-4.70 (3H, m), 5.20 (1H, d, J = 6.3Hz), 5.36 (1H, d, J = 7.3Hz),
5.43 (1H, d, J = 10.3Hz), 5.55 (1H, d, J = 17.1Hz), 5.93-6.08 (2H, m),
7.44 (2H, t, J = 7.3Hz), 7.54 (1H, t, J = 7.3Hz), 8.17 (2H, d, J = 7.3Hz).
[0617]
Step 5: 9 β-4-O-cyclopropanecarbonyl-4,10-dideacetyl-7-deoxy-9-dihydro-1-O-dimethylsilyl-9,10-O- (2-propenylidene) -13-O -Triethylsilylbaccatin III
The compound obtained in the above Step 4 was used as a raw material, and the same reaction operation as in Step 3 of Reference Example 11 was performed to obtain a white glassy title compound.
[0618]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.28 (3H, d, J = 3.0Hz), 0.05 (3H, d, J = 3.0Hz), 0.56-0.80 (6H, m),
1.02 (9H, t, J = 7.8Hz), 1.03-1.40 (4H, m), 1.21 (3H, s), 1.50-2.10 (5H, m),
1.51 (3H, s), 1.60 (3H, s), 1.90 (3H, s), 2.30 (2H, d, J = 8.8Hz),
2.83 (1H, d, J = 4.9Hz), 4.16 (1H, d, J = 8.3Hz), 4.22 (1H, d, J = 7.4Hz),
4.32 (1H, d, J = 8.3Hz), 4.60-4.72 (1H, m), 4.89 (1H, s), 5.01 (1H, t, J = 8.3Hz),
5.20 (1H, d, J = 8.3Hz), 5.26 (1H, d, J = 7.4Hz), 5.43 (1H, d, J = 10.3Hz),
5.55 (1H, d, J = 17.6Hz), 5.92-6.06 (2H, m), 7.45 (2H, t, J = 7.9Hz),
7.57 (1H, t, J = 7.9Hz), 8.11 (2H, d, J = 7.9Hz).
[0619]
Step 6: 9 β-4-O-cyclopropanecarbonyl-4,10-dideacetyl-7-deoxy-9-dihydro-9,10-O- (2-propenylidene) baccatin III
Using the compound obtained in Step 5 above as a raw material, the same reaction operation as in Step 3 of Reference Example 7 was carried out to obtain the title compound as a white glass.
[0620]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.08-1.24 (3H, m), 1.17 (3H, s), 1.34-1.41 (1H, m), 1.47 (3H, s),
1.60 (3H, s), 1.60-1.94 (5H, m), 1.97 (3H, s), 2.04-2.12 (1H, m),
2.37 (1H, d, J = 9.8Hz), 2.40 (1H, d, J = 11.7Hz), 3.07 (1H, d, J = 5.4Hz),
4.18 (1H, d, J = 6.8Hz), 4.27 (1H, d, J = 8.7Hz), 4.36 (1H, d, J = 8.7Hz),
4.69-4.82 (2H, m), 5.23 (1H, d, J = 6.3Hz), 5.33 (1H, d, J = 10.2Hz),
5.57 (1H, d, J = 17.1Hz), 5.96-6.08 (2H, m), 7.48 (2H, t, J = 7.3Hz),
7.60 (1H, t, J = 7.3Hz), 8.15 (2H, d, J = 7.3Hz).
[0621]
Reference Example 18
[0622]
Embedded image
Step 1: 9 β-4,10-dideacetyl-7-deoxy-9-dihydro-1-O-dimethylsilyl-4-O-ethoxycarbonyl-9,10-O- (2-propenylidene) -13-O— Triethylsilylbaccatin III
The compound obtained in Step 4 of Reference Example 17 was used as a raw material, and ethyl chloroformate was used instead of cyclopropanecarbonyl chloride, and the same reaction operation as in Step 3 of Reference Example 11 was performed. As a result, a colorless transparent oily title compound was obtained.
[0624]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
-0.28 (3H, d, J = 2.9Hz), 0.03 (3H, d, J = 2.9Hz), 0.56-0.75 (6H, m),
1.00 (9H, t, J = 7.8Hz), 1.22 (3H, s), 1.39 (3H, t, J = 7.3Hz), 1.50-1.70 (2H, m),
1.52 (3H, s), 1.60 (3H, s), 1.75-2.10 (2H, m), 1.89 (3H, s),
2.20-2.37 (2H, m), 2.80 (1H, d, J = 4.4Hz), 4.15-4.26 (3H, m),
4.36-4.44 (2H, m), 4.60-4.68 (1H, m), 4.98-5.04 (2H, m),
5.20 (1H, d, J = 6.3Hz), 5.26 (1H, d, J = 7.3Hz), 5.43 (1H, d, J = 10.3Hz),
5.55 (1H, d, J = 17.1Hz), 5.91-6.07 (2H, m), 7.45 (2H, t, J = 7.8Hz),
7.55 (1H, t, J = 7.8Hz), 8.13 (2H, d, J = 7.8Hz).
[0625]
Step 2: 9 β-4,10-dideacetyl-7-deoxy-9-dihydro-4-O-ethoxycarbonyl-9,10-O- (2-propenylidene) baccatin III
Using the compound obtained in Step 1 above as a raw material, the same reaction operation as in Step 3 of Reference Example 7 was carried out to obtain the title compound as a white glass.
[0626]
1H-NMR (400 MHz, CDClThree/ TMS) δ (ppm)
1.16 (3H, s), 1.43 (3H, t, J = 7.3Hz), 1.48 (3H, s), 1.54-2.15 (5H, m),
1.60 (3H, s), 1.97 (3H, s), 2.37 (1H, dd, J = 15.7Hz, J = 9.8Hz),
2.50 (1H, d, J = 10.3Hz), 3.00 (1H, d, J = 4.9Hz), 4.10-4.40 (5H, m),
4.65-4.80 (1H, m), 4.89 (1H, s), 5.23 (1H, d, J = 6.3Hz), 5.34 (1H, d, J = 6.9Hz),
5.46 (1H, d, J = 10.2Hz), 5.57 (1H, d, J = 17.1Hz), 5.92-6.08 (2H, m),
7.47 (2H, t, J = 7.8Hz), 7.58 (1H, t, J = 7.8Hz), 8.14 (2H, d, J = 7.8Hz).
[0627]
【The invention's effect】
The following experimental examples show the antitumor effect of the compounds of the present invention.
Experimental example
Three tumor cells, P388, PC-6 and PC-12, respectively,2 cells / 150 μl / well, PC-6 is 5.0 × 10Three cells / 150 μl / well, PC-12 is 1.0 × 10Three A 96-well microplate was seeded at cells / 150 μl / well, and P388 was added 2 hours later, and the other two samples were added 50 μl / well after 24 hours. Thereafter, the cells were cultured for 3 days, and a 5 mg / ml solution of MTT [3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyl-2H-tetrazolium bromide] was added at 20 μl / well. After 4 hours, the culture solution was removed, dimethyl sulfoxide was added at 150 μl / well, and the absorbance was measured at 540 nm. The antitumor effect is determined by the drug concentration at which the cell growth of the drug-added group is 50% of the control group50 It was shown as a value (ng / ml).
[0628]
[Table 8]
Claims (24)
Ｒ１はフェニル基を意味し、該フェニル基はハロゲン原子、アルキル基およびアルコキシル基からなる群から選ばれる基を置換基として１個または複数個有していてもよい。
Ｒ２はアルキル基、アルケニル基、アルキニル基、シクロアルキル基またはアルコキシル基を意味し、これらアルキル基、アルケニル基、アルキニル基、シクロアルキル基およびアルコキシル基は、ハロゲン原子、水酸基、カルボキシル基、アルコキシル基、アリールオキシ基、フェニル基、アミノ基、アルキルアミノ基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基およびアシルオキシ基からなる群から選ばれる基を置換基として１個または複数個有していてもよい。
Ｒ３は水素原子、水酸基、ハロゲン原子、アルコキシル基、基−Ｏ−Ｒ３１、アシルオキシ基または基−Ｏ−ＣＯ−Ｒ３１を意味し、該アルコキシル基およびアシルオキシ基は、ハロゲン原子、水酸基、カルボキシル基、シクロアルキル基、アルコキシル基、アリール基、アリールオキシ基、アミノ基、アルキルアミノ基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基、アシルオキシ基および複素環基（該複素環基は、その環の構成原子上にアルキル基を１個または複数個有してもよい。）からなる群から選ばれる基を置換基として１個または複数個有してもよい。
（ここで、Ｒ３１はアルキルアミノ基、アルケニル基、アルキニル基、シクロアルキル基、アリール基または複素環基を意味する。なお、これらアルキルアミノ基、アルケニル基、アルキニル基、シクロアルキル基、アリール基および複素環基は、ハロゲン原子、水酸基、カルボキシル基、アルキル基、アルコキシル基、アリールオキシ基、フェニル基、アミノ基、アルキルアミノ基、アミノアルキル基、アルキルアミノアルキル基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基、アシルオキシ基および３員環から８員環の大きさの含窒素複素環基（該含窒素複素環基は、その環の構成原子上にアルキル基を１個または複数個有してもよい。）からなる群から選ばれる基を置換基として１個または複数個有してもよい。）
また、Ｒ３はこれが結合している炭素原子に隣接する炭素原子に結合しているメチル基と共に３員環を形成してもよい。
Ｒ４およびＲ５は各々独立して、水素原子、アルキル基、アルケニル基、アルキニル基、アリール基または複素環基を意味し、これらアルキル基、アルケニル基、アルキニル基、アリール基および複素環基は、アルコキシル基、アミノ基、アルキルアミノ基、アミノアルキル基、アルキルアミノアルキル基および式
で表される、窒素原子を含む５員環から６員環の大きさの飽和の複素環基（該複素環基は、その環の構成原子である炭素原子上にアルキル基を１個または複数個有してもよい。）からなる群から選ばれる基を置換基として有してもよい。
また、Ｒ ４ およびＲ ５ は、Ｒ ４ 、Ｒ ５ およびこれらが結合している炭素原子と一緒になって、チオカルボニル基となってもよい。
Ｚ１は水素原子、水酸基、ハロゲン原子またはアルキル基を意味し、
Ｚ２は水素原子、水酸基、ハロゲン原子またはアルキル基を意味し、
Ｚ３はアルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基または複素環基を意味し、これらアルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基および複素環基は、ハロゲン原子、水酸基、カルボキシル基、アルキル基、アルコキシル基、フェニル基、アミノ基、アルキルアミノ基、アミノアルキル基、アルキルアミノアルキル基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基およびアシルオキシ基からなる群から選ばれる基を置換基として１個または複数個有してもよい。Ｚ４はアルキル基、アリール基またはアルコキシル基を意味し、これらアルキル基、アリール基およびアルコキシル基は、ハロゲン原子、水酸基、カルボキシル基、アルキル基、アルコキシル基、フェニル基、アミノ基、アルキルアミノ基、アミノアルキル基、アルキルアミノアルキル基、アルコキシカルボニル基、アリールオキシカルボニル基、アシル基、アシルアミノ基およびアシルオキシ基からなる群から選ばれる基を置換基として１個または複数個有してもよい。
なお、
で表される化合物およびその塩Formula (Ia)
R 1 represents a phenyl group, and the phenyl group may have one or more substituents selected from the group consisting of a halogen atom, an alkyl group and an alkoxyl group.
R 2 represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an alkoxyl group, and these alkyl group, alkenyl group, alkynyl group, cycloalkyl group and alkoxyl group are a halogen atom, a hydroxyl group, a carboxyl group and an alkoxyl group. , An aryloxy group, a phenyl group, an amino group, an alkylamino group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group, and one or more groups selected from the group consisting of an acyloxy group as a substituent It may be.
R 3 represents a hydrogen atom, a hydroxyl group, a halogen atom, an alkoxyl group, a group —O—R 31 , an acyloxy group or a group —O—CO—R 31 , and the alkoxyl group and the acyloxy group are a halogen atom, a hydroxyl group, a carboxyl, Group, cycloalkyl group, alkoxyl group, aryl group, aryloxy group, amino group, alkylamino group, alkoxycarbonyl group, aryloxycarbonyl group, acyl group, acylamino group, acyloxy group, and heterocyclic group (the heterocyclic group is And may have one or a plurality of alkyl groups on the constituent atoms of the ring.) A group selected from the group consisting of:
(Here, R 31 means an alkylamino group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group. These alkylamino groups, alkenyl groups, alkynyl groups, cycloalkyl groups, aryl groups) And a heterocyclic group includes a halogen atom, hydroxyl group, carboxyl group, alkyl group, alkoxyl group, aryloxy group, phenyl group, amino group, alkylamino group, aminoalkyl group, alkylaminoalkyl group, alkoxycarbonyl group, aryloxycarbonyl A group, an acyl group, an acylamino group, an acyloxy group, and a nitrogen-containing heterocyclic group having a size of 3 to 8 members (the nitrogen-containing heterocyclic group has one or more alkyl groups on the constituent atoms of the ring) One or a plurality of substituents selected from a group selected from the group consisting of (You may have one.)
R 3 may form a 3-membered ring with a methyl group bonded to a carbon atom adjacent to the carbon atom to which R 3 is bonded.
R 4 and R 5 each independently represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic group, and these alkyl group, alkenyl group, alkynyl group, aryl group and heterocyclic group are , Alkoxyl groups, amino groups, alkylamino groups, aminoalkyl groups, alkylaminoalkyl groups and formulas
And a saturated heterocyclic group having a size of 5 to 6-membered ring containing a nitrogen atom (wherein the heterocyclic group has one or more alkyl groups on a carbon atom that is a constituent atom of the ring) A group selected from the group consisting of: a substituent may be included.
R 4 and R 5 may be combined with R 4 , R 5 and the carbon atom to which they are bonded to form a thiocarbonyl group.
Z 1 represents a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group,
Z 2 means a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group,
Z 3 represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and these alkyl group, alkenyl group, alkynyl group, cycloalkyl group, aryl group and heterocyclic group are each a halogen atom. , Hydroxyl group, carboxyl group, alkyl group, alkoxyl group, phenyl group, amino group, alkylamino group, aminoalkyl group, alkylaminoalkyl group, alkoxycarbonyl group, aryloxycarbonyl group, acyl group, acylamino group and acyloxy group One or more groups selected from the group may be substituted. Z 4 means an alkyl group, an aryl group or an alkoxyl group, and these alkyl group, aryl group and alkoxyl group are a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxyl group, a phenyl group, an amino group, an alkylamino group, One or more groups selected from the group consisting of an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group, and an acyloxy group may be included as a substituent.
In addition,
And a salt thereof
（これらアルキル基、アルケニル基またはフェニル基は、アルコキシル基、アミノ基、アルキルアミノ基、および式
で表される窒素原子を含む５員環から６員環の大きさの飽和の複素環基（該複素環基は、その環の構成原子である炭素原子上にアルキル基を１個または複数個有してもよい。）からなる群から選ばれる基を置換基として１個または複数個有してもよい。）
である請求項１記載の化合物およびその塩R 4 or R 5 is an alkyl group, an alkenyl group or a phenyl group (the alkyl group, alkenyl group or phenyl group, A Rukokishiru group, amino group, an alkylamino group, Contact and expression
A saturated heterocyclic group having a size of 5 to 6 members containing a nitrogen atom represented by the formula (the heterocyclic group includes one or a plurality of alkyl groups on a carbon atom that is a constituent atom of the ring). One or more groups selected from the group consisting of: a substituent may be included. )
The compound according to claim 1 and a salt thereof
で表される窒素原子を含む５員環から６員環の大きさの飽和の複素環基（該複素環基は、その環の構成原子である炭素原子上にアルキル基を１個または複数個有してもよい。）である請求項２０記載の化合物およびその塩The substituent of the alkyl group, alkenyl group or phenyl group of R 4 or R 5 is an amino group, an alkylamino group or a formula
A saturated heterocyclic group having a size of 5 to 6 members containing a nitrogen atom represented by the formula (the heterocyclic group includes one or a plurality of alkyl groups on a carbon atom that is a constituent atom of the ring). 21. The compound according to claim 20 and a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10661596A JP3746563B2 (en) | 1995-04-28 | 1996-04-26 | Pentacyclic compound |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7-106295 | 1995-04-28 | ||
| JP10629595 | 1995-04-28 | ||
| JP10661596A JP3746563B2 (en) | 1995-04-28 | 1996-04-26 | Pentacyclic compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0912578A JPH0912578A (en) | 1997-01-14 |
| JP3746563B2 true JP3746563B2 (en) | 2006-02-15 |
Family
ID=26446415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10661596A Expired - Fee Related JP3746563B2 (en) | 1995-04-28 | 1996-04-26 | Pentacyclic compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3746563B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1741716T3 (en) | 2004-04-30 | 2011-11-28 | Daiichi Sankyo Co Ltd | Process for the preparation of pentacyclic taxane |
| JPWO2007049575A1 (en) * | 2005-10-25 | 2009-04-30 | 第一三共株式会社 | Taxane compound having azetidine ring structure |
| WO2008117775A1 (en) * | 2007-03-27 | 2008-10-02 | Daiichi Sankyo Company, Limited | Taxanes having oxetane ring structure |
-
1996
- 1996-04-26 JP JP10661596A patent/JP3746563B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0912578A (en) | 1997-01-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6545151B2 (en) | Pentacyclic compound | |
| WO1998022451A1 (en) | Taxol derivatives | |
| JP4823456B2 (en) | Taxane derivative and method for producing the same | |
| JP3746563B2 (en) | Pentacyclic compound | |
| US5767296A (en) | Deacetoxytaxol derivatives | |
| US5608073A (en) | Baccatin derivatives and processes for preparing the same | |
| JPWO1996033998A1 (en) | pentacyclic compound | |
| US5347007A (en) | Method of preparing 7-oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs useful in the treatment of thrombotic and vasospastic disease | |
| JPWO2007049575A1 (en) | Taxane compound having azetidine ring structure | |
| WO1996023779A1 (en) | Ether derivative | |
| JP3921252B2 (en) | Ether derivatives | |
| HK1008529B (en) | Pentacyclic compounds | |
| JP3784945B2 (en) | Taxol derivative | |
| US5260448A (en) | Method for preparing 7-oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs useful in the treatment of thrombotic and vasospastic disease | |
| JP3699156B2 (en) | Deacetoxytaxol derivative | |
| JPH08253465A (en) | Tetracyclic compound | |
| JPH09208572A (en) | 18-site-substituted taxol derivative | |
| JPWO1998022451A1 (en) | Taxol derivatives | |
| KR20220166828A (en) | Meyamaisin Analogs and Methods of Use Thereof | |
| JPWO1999032473A1 (en) | Taxane derivatives | |
| TW200842126A (en) | Taxane compound having azetidine ring structure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20050614 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050801 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20051115 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20051124 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081202 Year of fee payment: 3 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081202 Year of fee payment: 3 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081202 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20091202 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20091202 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101202 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101202 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101202 Year of fee payment: 5 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111202 Year of fee payment: 6 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111202 Year of fee payment: 6 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121202 Year of fee payment: 7 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121202 Year of fee payment: 7 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131202 Year of fee payment: 8 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: R3D03 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |