JPH0120148B2 - - Google Patents
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- Publication number
- JPH0120148B2 JPH0120148B2 JP55185539A JP18553980A JPH0120148B2 JP H0120148 B2 JPH0120148 B2 JP H0120148B2 JP 55185539 A JP55185539 A JP 55185539A JP 18553980 A JP18553980 A JP 18553980A JP H0120148 B2 JPH0120148 B2 JP H0120148B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- imino
- tetrahydropyranyl
- amino
- acid
- 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
Links
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- -1 γ-aminobutyric acid ester Chemical class 0.000 claims description 11
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutanoic acid Natural products NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 5
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims description 4
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000006268 reductive amination reaction Methods 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 238000006578 reductive coupling reaction Methods 0.000 claims 1
- 239000002253 acid Substances 0.000 description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 8
- GJRGEVKCJPPZIT-JBDRJPRFSA-N mugineic acid Chemical compound OC(=O)[C@@H](O)CCN[C@H](C(O)=O)[C@@H](O)CN1CC[C@H]1C(O)=O GJRGEVKCJPPZIT-JBDRJPRFSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- GJRGEVKCJPPZIT-UHFFFAOYSA-N isomugineic acid Natural products OC(=O)C(O)CCNC(C(O)=O)C(O)CN1CCC1C(O)=O GJRGEVKCJPPZIT-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- QUKMQOBHQMWLLR-MGURRDGZSA-N 4-[[(1S)-1-carboxy-3-hydroxypropyl]amino]-2-[(3-carboxy-3-hydroxypropyl)amino]butanoic acid Chemical compound OCC[C@H](NCCC(NCCC(O)C(O)=O)C(O)=O)C(O)=O QUKMQOBHQMWLLR-MGURRDGZSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 4
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 229930195135 Avenic acid Natural products 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- IADUEWIQBXOCDZ-VKHMYHEASA-N Azetidine-2-carboxylic acid Natural products OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- NPLXMOUPIRQAGN-UHFFFAOYSA-N benzyl azetidine-2-carboxylate Chemical compound C1CNC1C(=O)OCC1=CC=CC=C1 NPLXMOUPIRQAGN-UHFFFAOYSA-N 0.000 description 2
- 229930002875 chlorophyll Natural products 0.000 description 2
- 235000019804 chlorophyll Nutrition 0.000 description 2
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 150000003138 primary alcohols Chemical group 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical class O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 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
- 206010022971 Iron Deficiencies Diseases 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000005708 tetrahydropyranylation reaction Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Furan Compounds (AREA)
- Pyrane Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、ムギネ酸、2′−デオキシムギネ酸、
及びアベニン酸等のムギネ酸類の合成における重
要な新規な中間体、並びにその新規な製造法に関
するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention provides mugineic acid, 2'-deoxymuginic acid,
The present invention relates to important new intermediates in the synthesis of mugineic acids such as abenic acid and abenic acid, and a new method for producing the same.
植物が、その成長及び生命を維持するために、
多くの元素を必要とすることが知られている。例
えば、鉄は、クロロフイルの生合成に必要であ
り、鉄不足は、鉄性黄変病をひき起す。 In order for plants to maintain their growth and life,
It is known that many elements are required. For example, iron is required for chlorophyll biosynthesis, and iron deficiency causes iron yellowing disease.
最近、稲の根の水耕液からムギネ酸〔11〕が、
小麦から２−デオキシムギネ酸〔12〕が、また、
からす麦からアベニン酸〔13〕が発見された。 Recently, mugineic acid [11] has been extracted from the hydroponic solution of rice roots.
2-deoxymuginic acid [12] is also obtained from wheat.
Avenic acid [13] was discovered in barley.
また、最近の研究によれば、ムギネ酸又は2′−
デオキシムギネ酸を、水耕裁培の水溶液中に添加
することによつて、稲のクロロフイル含量を増加
させることができることが、明らかになつた。 Also, according to recent research, mugineic acid or 2′-
It has been revealed that the chlorophyll content of rice can be increased by adding deoxymuginic acid to an aqueous solution of hydroponic cultivation.
更に、これらの化合物を詳細に研究したとこ
ろ、低分子量であるにも拘らず、銅等の金属に配
位し、キレート化合物を形成することが、明らか
になつた。このような観点からみれば、これらの
ムギネ酸類は、最小の分子量を有するキレート剤
であつて、将来、多くの新しい用途が期待される
重要な化合物であるといえる。 Furthermore, detailed studies of these compounds revealed that, despite their low molecular weight, they coordinate with metals such as copper to form chelate compounds. From this point of view, these mugineic acids are chelating agents with the smallest molecular weight, and can be said to be important compounds that are expected to have many new uses in the future.
本発明者は、これらムギネ酸類の合成法につい
て、鋭意研究の結果、その全合成に成功した。 As a result of intensive research into the synthesis method of these mugineic acids, the present inventors succeeded in the total synthesis thereof.
そして、その過程において、新規な重要な中間
体に関する本発明を完成した。 In the process, the present invention relating to a new important intermediate was completed.
ムギネ酸類は、次のような工程によつて合成さ
れる。 Mugineic acids are synthesized through the following steps.
ａ−ヒドロキシ−γ−ブチロラクトン誘導体
〔14〕を、開環すると同時にカルボキシル基をベ
ンジルエステル化して、ａ−テトラヒドロピラノ
キシ−γ−ヒドロキシ酪酸ベンジル〔15〕を作
る。 Benzyl a-tetrahydropyranoxy-γ-hydroxybutyrate [15] is produced by ring-opening the a-hydroxy-γ-butyrolactone derivative [14] and at the same time converting the carboxyl group into a benzyl ester.
更に、その末端の第１アルコールをピリジニウ
ムクロロクロメートによりアルデヒド〔16〕に酸
化し、ａ−アミノ−γ−ブチロラクトン誘導体
〔17〕と本発明の方法によりカプリングし、γ−
アミノ−ａ−テトラヒドロピラノキシ酪酸ベンジ
ル誘導体〔18〕を作る。 Furthermore, the terminal primary alcohol is oxidized to aldehyde [16] with pyridinium chlorochromate, and coupled with a-amino-γ-butyrolactone derivative [17] by the method of the present invention to form γ-
Prepare benzyl amino-a-tetrahydropyranoxybutyrate derivative [18].
イミノ基を保護した後〔19〕、開環すると同時
にベンジルエステル化して、γ−ヒドロキシ酪酸
エステル誘導体〔20〕を作る。 After protecting the imino group [19], the ring is opened and simultaneously benzyl esterified to produce a γ-hydroxybutyric acid ester derivative [20].
更に、その末端の第１アルコールをピリジニウ
ムクロロメートによりアルデヒド〔21〕に酸化
し、例えば、アゼチジン−２−カルボン酸エステ
ル〔22〕と本発明の方法によりカツプリングし、
イミノ基、ヒドロキシル基及びカルボキシル基
を、tert.ブトキシカルボニル基、テトラヒドロピ
ラニル基及びベンジル基で、それぞれ保護した
2′−デオキシムギネ酸〔23〕を作る。 Furthermore, the terminal primary alcohol is oxidized to aldehyde [21] with pyridinium chloromate, and coupled with, for example, azetidine-2-carboxylic acid ester [22] by the method of the present invention,
The imino group, hydroxyl group and carboxyl group are protected with tert.butoxycarbonyl group, tetrahydropyranyl group and benzyl group, respectively.
Make 2′-deoxymuginic acid [23].
次いで、温和な条件で、イミノ基、ヒドロキシ
ル基及びカルボキシル基の保護基を外して、2′−
デオキシムギネ酸〔12〕をうる。 Next, under mild conditions, the protecting groups of the imino group, hydroxyl group, and carboxyl group are removed to give 2′-
Obtain deoxymuginic acid [12].
なお、ａ−アミノ−γ−ブチロラクトン誘導体
〔17〕の代りに、ａ−アミノ−β−ヒドロキシ−
γ−ブチロラクトン誘導体〔24〕を用いれば、ム
ギネ酸〔11〕をうることができる。 Note that instead of the a-amino-γ-butyrolactone derivative [17], a-amino-β-hydroxy-
By using the γ-butyrolactone derivative [24], mugineic acid [11] can be obtained.
また、アゼチジン−２−カルボン酸エステル
〔22〕の代りに、ａ−アミノ−γ−ヒドロキシ酪
酸エステル誘導体〔25〕を用いれば、アベニン酸
〔13〕をうることができる。 Furthermore, abenic acid [13] can be obtained by using an a-amino-γ-hydroxybutyric acid ester derivative [25] instead of azetidine-2-carboxylic acid ester [22].
本発明は、このムギネ酸類の合成方法におい
て、特に重要な中間体であるγアミノ酪酸エステ
ル誘導体〔１〕及びその合成法に関するものであ
る。 The present invention relates to a γ-aminobutyric acid ester derivative [1], which is a particularly important intermediate in the method for synthesizing mugineic acids, and a method for synthesizing the same.
ここで、ｎは０〜３のくり返し数を表わし、
R1R3〜R5、R2は、それぞれ水素又はテトラヒド
ロピラニル基等によつて保護されたヒドロキシル
基を表わし、Ａは、次式〔２〕、〔３〕又は〔４〕
に示したようなアミノ基又はイミノ基の窒素で結
合している基を表わし、Ｂはtert.ブトキシカルボ
ニル基等のイミノ基の保護基を表わす。 Here, n represents the number of repetitions from 0 to 3,
R 1 R 3 to R 5 and R 2 each represent a hydroxyl group protected by hydrogen or a tetrahydropyranyl group, and A is represented by the following formula [2], [3] or [4]
B represents a group bonded to the nitrogen of an amino group or an imino group as shown in , and B represents a protecting group for the imino group such as a tert.butoxycarbonyl group.
このγアミノ酪酸エステル誘導体〔１〕には、
ムギネ酸、2′−デオキシムギネ酸及びアベニン酸
の中間体であるγ−アミノ−ａ−ヒドロキシ酪酸
エステル誘導体〔18〕、イミノ基、ヒドロキシル
基及びカルボキシル基を、tert.ブトキシカルボニ
ル基、テトラヒドロピラニル基及びベンジル基
で、それぞれ保護したムギネ酸〔26〕、2′−デオ
キシムギネ酸〔23〕及びアベニン酸〔27〕が含ま
れるが、必ずしもこれらのものに限定されるもの
ではない。 This γ-aminobutyric acid ester derivative [1] includes:
γ-Amino-a-hydroxybutyric acid ester derivative [18] which is an intermediate of mugineic acid, 2'-deoxymuginic acid and avenic acid, imino group, hydroxyl group and carboxyl group, tert.butoxycarbonyl group, tetrahydropyranyl group and mugineic acid [26], 2'-deoxymuginic acid [23], and avenic acid [27] protected with a benzyl group, respectively, but are not necessarily limited to these.
ムギネ酸類の合成は、ラセミ化を避けるため、
温和な条件で反応させることが必要であり、イミ
ノ基、ヒドロキシル基又はカルボキシル基等の保
護基も、その導入及び除去が温和な条件で行える
ものでなければならない。 In the synthesis of mugineic acids, to avoid racemization,
It is necessary to carry out the reaction under mild conditions, and protecting groups such as imino groups, hydroxyl groups, or carboxyl groups must also be capable of being introduced and removed under mild conditions.
このような観点から、鋭意研究の結果、イミノ
基はtert.ブトキシカルボニル化し、ヒドロキシル
基はテトラヒドロピラニル化し、カルボキシル基
はベンジルエステル化することが最も適している
ことが、明らかになつた。特にカルボキシル基に
ついては、ベンジルエステル化する以外に、本目
的に適した方法は発見できなかつた。 From this point of view, as a result of intensive research, it has become clear that it is most suitable to convert imino groups into tert.butoxycarbonylation, to convert hydroxyl groups into tetrahydropyranylation, and to convert carboxyl groups into benzyl esters. In particular, regarding carboxyl groups, no method suitable for this purpose could be found other than benzyl esterification.
本願発明のγアミノ酪酸エステル誘導体は、こ
のような目的に合致するものであり、かつ、ムギ
ネ酸類の一連の合成工程において、式〔18〕及び
式〔26〕、〔23〕又は〔27〕に示したように、くり
返し合成される極めて重要な中間体である。 The γ-aminobutyric acid ester derivatives of the present invention meet these objectives, and can be expressed by formula [18] and formula [26], [23] or [27] in a series of steps for synthesizing mugineic acids. As shown, it is an extremely important intermediate that is repeatedly synthesized.
また、この中間体について、鋭意研究の結果、
一般式〔５〕に表わされるアルデヒドと、式
〔６〕、〔７〕もしくは〔８〕に示すようなアミノ
化合物もしくはイミノ化合物又はそれらの塩と
を、メタノール等の溶媒中で、シアノ硼水素化ナ
トリウム（NaBH3CH）等の還元剤により、還
元アミノ化し、カプリングすることによつて、こ
の中間体を初めて合成することに成功した。 In addition, as a result of intensive research on this intermediate,
An aldehyde represented by the general formula [5] and an amino compound or imino compound or a salt thereof as shown in the formula [6], [7] or [8] are subjected to cyanoborohydride in a solvent such as methanol. For the first time, we succeeded in synthesizing this intermediate by reductive amination with a reducing agent such as sodium (NaBH 3 CH) and coupling.
ここで、ｎは０〜３のくり返し数を表わし、
R1R2、R3〜R5は、それぞれ水素又はテトラヒド
ロピラニル基等によつて保護されたヒドロキシル
基を表わし、Ｂはtert.ブトキシカルボニル基等の
イミノ基の保護基を表わす。 Here, n represents the number of repetitions from 0 to 3,
R 1 R 2 and R 3 to R 5 each represent a hydroxyl group protected by hydrogen or a tetrahydropyranyl group, and B represents a protecting group for an imino group such as a tert.butoxycarbonyl group.
実施例 １
ａ−アミノ−γ−ブチロラクトンのトリフルオ
ロ酢酸塩〔28〕930mg、4.32ミリモル、1.5ミリグ
ラム当量を溶解した乾燥メタノール溶液20mlに、
０℃、窒素の雰囲気中で、ａ−テトラヒドロピラ
ノキシ−β−フオルミルプロピオン酸ベンジル
〔29〕846mg、2.88ミリモルを溶解したメタノール
溶液５mlを加え、次いで、シアノ硼水素化ナトリ
ウム（Sodium cyanoborohydride NaBH3CN）
189mgを加え、30分撹拌した。その後、室温まで
温め、14時間撹拌した。反応混合物に水10mlを加
えて急冷し、溶媒を減圧で吸引除去した。その
後、CHCl3で３回抽出し、NgSo4上で乾燥し、溶
媒を減圧で吸引除去して油状物質をえた。これ
を、Silic CC7を用いたカラムクロマトグラムに
より、エチルエーテルで展開し、ａ−テトラヒド
ロピアノキシ−γ−テトラヒドロフラノアミノ酪
酸ベンジル〔30〕977mgをえた。収率約90％。Example 1 Trifluoroacetate of a-amino-γ-butyrolactone [28] 930 mg, 4.32 mmol, 1.5 milligram equivalents were dissolved in 20 ml of dry methanol solution.
At 0°C and in a nitrogen atmosphere, 5 ml of a methanol solution containing 846 mg (2.88 mmol) of benzyl a-tetrahydropyranoxy-β-formylpropionate [29] was added, and then sodium cyanoborohydride (sodium cyanoborohydride) was added. NaBH3CN )
189 mg was added and stirred for 30 minutes. Then, it was warmed to room temperature and stirred for 14 hours. The reaction mixture was quenched by adding 10 ml of water, and the solvent was suctioned off under reduced pressure. It was then extracted three times with CHCl 3 , dried over NgSo 4 and the solvent was removed under reduced pressure to give an oil. This was subjected to column chromatography using Silic CC7 and developed with ethyl ether to obtain 977 mg of benzyl a-tetrahydropianoxy-γ-tetrahydrofuranoaminobutyrate [30]. Yield approximately 90%.
実施例 ２
アゼチジン−２−カルボン酸ベンジルのトリフ
ルオロ酢酸塩〔31〕46mg、0.15ミリモルを溶解し
た乾燥メタノール１mlに、０℃、窒素の雰囲気中
で、ａ−アミノ−β−フオルミルプロピオン酸ベ
ンジル誘導体〔32〕50mg、0.91ミリモルを溶解し
たメタノール溶液を加え、次いで、シアノ硼水素
化ナトリウム（Sodium cyanoborohydride
NaBH3CN）7.0mg、1.1ミリモルを加えた。１時
間後に室温まで温め、16時間撹拌した。反応混合
物を水５c.c.の中に注ぎ急冷し、溶媒を減圧で吸引
除去した。粗生成物をCHCl3で３回抽出し、抽出
物を集めてMgSo4上で乾燥し、溶媒を減圧で吸
引除去して油状物質をえ、これをSilic CC7を用
いたカラムクロマトグラムにより、エチルエーテ
ル・ｎヘキサン（１：１）で展開し、ａ−アミノ
−γ−イミノ酪酸ベンジル誘導体〔33〕41mgをえ
た。収率約60％。 Example 2 Trifluoroacetate of benzyl azetidine-2-carboxylate [31] 46 mg, 0.15 mmol was dissolved in 1 ml of dry methanol at 0° C. in a nitrogen atmosphere to a-amino-β-formylpropionic acid. A methanol solution containing 50 mg, 0.91 mmol of benzyl derivative [32] was added, and then sodium cyanoborohydride (Sodium cyanoborohydride) was added.
NaBH3CN ) 7.0 mg, 1.1 mmol was added. After 1 hour, the mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was quenched by pouring into 5 c.c. of water and the solvent was removed under reduced pressure. The crude product was extracted three times with CHCl3 , the combined extracts were dried over MgSo4 , and the solvent was removed under reduced pressure to give an oil, which was analyzed by column chromatography using Silic CC7 in ethyl The mixture was developed with ether/n-hexane (1:1) to obtain 41 mg of benzyl a-amino-γ-iminobutyric acid derivative [33]. Yield approximately 60%.
なお、化合物〔29〕、〔30〕、〔32〕及び〔33〕の
IR、NMR等のデータは、次のとおりであり、上
記実施例の結果を裏づけている。 In addition, compounds [29], [30], [32] and [33]
The data of IR, NMR, etc. are as follows, and support the results of the above examples.
式〔29〕の化合物
IR（CHCl3）1738、1730cm-1
1H NMR（CDCl3）δ9.76（ｔ、1H、Ｊ＝２Hz）、
7.43（Ｓ、5H）、5.19（ｓ、2H）、4.84（ｔ、1H、Ｊ
＝８Hz）、2.86（dd、2H、Ｊ＝２、８Hz）
式〔30〕の化合物
IR（CHCl3）3300、1775、1736cm-1
1H NMR（CDCl3）δ7.35（Ｓ、5H）、5.20（ｄ、
1H、Ｊ＝12Hz）5.12（ｄ、1H、Ｊ＝12Hz）、4.50
（ｔ、1H、Ｊ＝７Hz）
Mass spectrum、ｍ／e292（M+−THP）
式〔32〕の化合物
IR（CHCl3）2725、1743、1735、1695cm-1
1H NMR（CDCl3）δ9.76（bs、1H）、7.32（Ｓ、
5H）、7.28（Ｓ、5H）
5.12（Ｓ、4H）、4.28〜4.68（ｍ、3H）、1.35（Ｓ、
9H）
式〔33〕の化合物
IR（CHCl3）1740、1690cm-1
1H NMR（CDCl3 at50℃）δ7.30（ｓ、10H）、
7.27（ｓ、5H）、5.20（ｄ、1H、Ｊ＝12Hz）、5.11
（ｓ、4H）、5.06（ｄ、1H、Ｊ＝12Hz）、1.35（ｓ、
9H）
Mass spectrum、ｍ／e759（M+＋１）Compound of formula [29] IR (CHCl 3 ) 1738, 1730 cm -1 1 H NMR (CDCl 3 ) δ9.76 (t, 1H, J = 2Hz),
7.43 (S, 5H), 5.19 (s, 2H), 4.84 (t, 1H, J
= 8 Hz), 2.86 (dd, 2H, J = 2, 8 Hz) Compound IR (CHCl 3 ) 3300, 1775, 1736 cm -1 1 H NMR (CDCl 3 ) δ7.35 (S, 5H) of formula [30], 5.20(d,
1H, J=12Hz) 5.12 (d, 1H, J=12Hz), 4.50
(t, 1H, J=7Hz) Mass spectrum, m/e292 (M + -THP) Compound IR (CHCl 3 ) of formula [32] 2725, 1743, 1735, 1695 cm -1 1 H NMR (CDCl 3 ) δ9. 76 (BS, 1H), 7.32 (S,
5H), 7.28 (S, 5H) 5.12 (S, 4H), 4.28~4.68 (m, 3H), 1.35 (S,
9H) Compound of formula [33] IR (CHCl 3 ) 1740, 1690 cm -1 1 H NMR (CDCl 3 at 50°C) δ7.30 (s, 10H),
7.27 (s, 5H), 5.20 (d, 1H, J=12Hz), 5.11
(s, 4H), 5.06 (d, 1H, J=12Hz), 1.35 (s,
9H) Mass spectrum, m/e759 (M + +1)
Claims (1)
ステル誘導体。 ここで、ｎは０〜２のくり返し数を表し、R1、
R2、R3（Ro+2でｎ＝１）、R4（Ro+2でｎ＝２）は、
それぞれ、水素、又はテトラヒドロピラニル基等
によつて保護されたヒドロキシル基を表し、Ａは
次式〔２〕〔３〕又は〔４〕に示したようなアミ
ノ基又はイミノ基の窒素で結合している基を表
し、Ｂはtert−ブトキシカルボニル基等のイミノ
基の保護基を表す。 ここで、R5は水素、又はテトラヒドロピラニ
ル基等によつて保護されたヒドロキシル基を表
す。 ２ 下記一般式〔５〕で表されるアルデヒドと、
次式〔６〕〔７〕もしくは〔８〕に示すようなア
ミノ化合物もしくはイミノ化合物又はそれらの塩
とを、メタノール等の溶媒中で、シアノ硼水素化
ナトリウム（NaBH3CN）等の還元剤により還
元アミノ化し、カプリングして、下記一般式
〔９〕で表されるγアミノ酪酸誘導体を製造する
方法。 ここで、ｎは０〜２のくり返し数を表し、R1、
R2、R3（Ro+2でｎ＝１）、R4（Ro+2でｎ＝２）、R5
は、それぞれ、水素、又はテトラヒドロピラニル
基等によつて保護されたヒドロキシル基を表し、
Ａは次式〔10〕〔11〕又は〔12〕に示したような
アミノ基又はイミノ基の窒素で結合している基を
表し、Ｂはtert−ブトキシカルボニル基等のイミ
ノ基の保護基を表し、THPはテトラヒドロピラ
ニル基を表す。 ここで、R5は水素、又はテトラヒドロピラニ
ル基等によつて保護されたヒドロキシル基を表
し、THPはテトラヒドロピラニル基を表す。[Scope of Claims] 1. A γ-aminobutyric acid ester derivative represented by the following general formula [1]. Here, n represents the number of repetitions from 0 to 2, R 1 ,
R 2 , R 3 (n=1 at R o+2 ), R 4 (n=2 at R o+2 ) are
Each represents hydrogen or a hydroxyl group protected by a tetrahydropyranyl group, etc., and A is bonded with the nitrogen of an amino group or imino group as shown in the following formula [2] [3] or [4]. B represents a group protecting an imino group such as a tert-butoxycarbonyl group. Here, R 5 represents hydrogen or a hydroxyl group protected by a tetrahydropyranyl group or the like. 2 an aldehyde represented by the following general formula [5],
An amino compound or imino compound or a salt thereof as shown in the following formula [6] [7] or [8] is mixed with a reducing agent such as sodium cyanoborohydride (NaBH 3 CN) in a solvent such as methanol. A method for producing a γ-aminobutyric acid derivative represented by the following general formula [9] by carrying out reductive amination and coupling. Here, n represents the number of repetitions from 0 to 2, R 1 ,
R 2 , R 3 (n=1 at R o+2 ), R 4 (n=2 at R o+2 ), R 5
each represents a hydroxyl group protected by hydrogen or a tetrahydropyranyl group,
A represents a group bonded to the nitrogen of an amino group or an imino group as shown in the following formula [10] [11] or [12], and B represents a protecting group for the imino group such as a tert-butoxycarbonyl group. and THP represents a tetrahydropyranyl group. Here, R 5 represents hydrogen or a hydroxyl group protected by a tetrahydropyranyl group or the like, and THP represents a tetrahydropyranyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP55185539A JPS57112369A (en) | 1980-12-29 | 1980-12-29 | Intermediate of mugineic acids and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP55185539A JPS57112369A (en) | 1980-12-29 | 1980-12-29 | Intermediate of mugineic acids and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57112369A JPS57112369A (en) | 1982-07-13 |
| JPH0120148B2 true JPH0120148B2 (en) | 1989-04-14 |
Family
ID=16172570
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP55185539A Granted JPS57112369A (en) | 1980-12-29 | 1980-12-29 | Intermediate of mugineic acids and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57112369A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7108905B2 (en) | 2000-02-22 | 2006-09-19 | Ronald H. Ball | Protective film for the surface of a handrail for an escalator or moving walkway |
| US6682806B1 (en) | 1999-02-19 | 2004-01-27 | Ronald H. Ball | Method of applying a protective film, optionally including advertising or other visible material, to the surface of a handrail for an escalator or moving walkway |
| US7278528B2 (en) | 1999-02-19 | 2007-10-09 | Ronald H. Ball | Method of and apparatus for applying a film optionally including advertising or other visible material, to the surface of a handrail for an escalator or moving walkway |
-
1980
- 1980-12-29 JP JP55185539A patent/JPS57112369A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57112369A (en) | 1982-07-13 |
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