JPH027592B2 - - Google Patents
Info
- Publication number
- JPH027592B2 JPH027592B2 JP3795583A JP3795583A JPH027592B2 JP H027592 B2 JPH027592 B2 JP H027592B2 JP 3795583 A JP3795583 A JP 3795583A JP 3795583 A JP3795583 A JP 3795583A JP H027592 B2 JPH027592 B2 JP H027592B2
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- uracil
- solvent
- compound
- bromo
- 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
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Natural products O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 20
- 229940035893 uracil Drugs 0.000 claims description 12
- -1 uracil nucleoside Chemical class 0.000 claims description 11
- 239000002777 nucleoside Substances 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 238000012746 preparative thin layer chromatography Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000006114 decarboxylation reaction Methods 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- GCQYYIHYQMVWLT-HQNLTJAPSA-N Sorivudine Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(\C=C\Br)=C1 GCQYYIHYQMVWLT-HQNLTJAPSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003729 cation exchange resin Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- VRIUYSDAKYHMAA-UHFFFAOYSA-N ethyl 2-[(2-bromophenyl)-diphenyl-lambda5-phosphanylidene]acetate Chemical compound BrC1=C(C=CC=C1)P(C1=CC=CC=C1)(C1=CC=CC=C1)=CC(=O)OCC VRIUYSDAKYHMAA-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
- MZBPLEJIMYNQQI-JAGXHNFQSA-N 1-[(2r,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidine-5-carbaldehyde Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C=O)=C1 MZBPLEJIMYNQQI-JAGXHNFQSA-N 0.000 description 1
- HXDYHJGZXSPLJE-UHFFFAOYSA-N 2,4-dioxopyrimidine-1-carbaldehyde Chemical compound O=CN1C=CC(=O)NC1=O HXDYHJGZXSPLJE-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- ODZBBRURCPAEIQ-DJLDLDEBSA-N Brivudine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C=CBr)=C1 ODZBBRURCPAEIQ-DJLDLDEBSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、新規物質である５−（２−カルボキ
シ−２−ハロゲノビニル）ウラシルヌクレオシド
に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel substance, 5-(2-carboxy-2-halogenovinyl)uracil nucleoside.
本発明化合物である５−（２−カルボキシ−２
−ハロゲノビニル）ウラシルヌクレオシドは一般
式〔〕で示される化合物を総称する。 The compound of the present invention, 5-(2-carboxy-2
-halogenovinyl) uracil nucleoside is a general term for compounds represented by the general formula [].
該式中、R1は水素または水酸基を示し、Ｘは
ハロゲンを示す。Ｘのハロゲンの具体例は臭素、
塩素、またはヨウ素である。以下、本発明化合物
を５−（２−カルボキシ−２−ハロゲノビニル）
Usと略称することがある。 In this formula, R 1 represents hydrogen or a hydroxyl group, and X represents halogen. Specific examples of halogen for X are bromine,
Chlorine or iodine. Hereinafter, the compound of the present invention will be described as 5-(2-carboxy-2-halogenovinyl)
Sometimes abbreviated as Us.
５−（２−カルボキシ−２−ハロゲノビニル）
Usは、それを脱炭酸反応に供することにより、
容易に強力な抗ウイルス活性を有する化合物とし
て公知の５−（２−ブロモビニル）−１−β−Ｄ−
2′−デオキシリボフラノシルウラシル（BVDU）、
１−β−Ｄ−アラビノフラノシル−５−（２−ブ
ロモビニル）ウラシル（BVAU）、１−β−Ｄ−
アラビノフラノシル−５−（２−クロロビニル）
ウラシル（CVAU）などに導くことができる。
本発明化合物はこれら抗ウイルス性化合物を製造
する上できわめて重要な合成中間体である。 5-(2-carboxy-2-halogenovinyl)
By subjecting it to a decarboxylation reaction, Us
5-(2-bromovinyl)-1-β-D-, which is easily known as a compound with strong antiviral activity.
2′-deoxyribofuranosyluracil (BVDU),
1-β-D-arabinofuranosyl-5-(2-bromovinyl)uracil (BVAU), 1-β-D-
Arabinofuranosyl-5-(2-chlorovinyl)
It can lead to Uracil (CVAU) etc.
The compounds of the present invention are extremely important synthetic intermediates for producing these antiviral compounds.
本発明化合物の調製にあたつては、特にその製
造ルートに制約されるものではなく、本発明化合
物の合成にあたつてデザインされうるあらゆる化
学合成的手法が採用できる。製造法を具体的に提
示すれば次のような方法が挙げられる。 In preparing the compound of the present invention, there are no particular restrictions on the production route, and any chemical synthesis method that can be designed for the synthesis of the compound of the present invention can be employed. Specific manufacturing methods include the following methods.
すなわち、一般式〔〕
〔式中、R1は水素または水酸基を示す。〕で表わ
される５−ホルミルウラシルヌクレオシドに一般
式〔〕
（R2）3P＝CXCOOR3 〔〕
〔式中、R2はアルキル基および／またはアリー
ル基を示し、R3はアルキル基またはアリール基
を示し、Ｘはハロゲンを示す。〕で表わされるホ
スホランを反応させて一般式〔〕
〔式中、R1、R3およびＸは前記と同意義であ
る。〕で表わされる５−（２−アルコキシもしくは
アロキシカルボニル−２−ハロゲンビニル）ウラ
シルヌクレオシドを得、次いでこれを加水分解す
る方法によつて本発明化合物を合成することがで
きる。 In other words, the general formula [] [In the formula, R 1 represents hydrogen or a hydroxyl group. 5-formyluracil nucleoside represented by the general formula [] (R 2 ) 3 P=CXCOOR 3 [] [In the formula, R 2 represents an alkyl group and/or an aryl group, and R 3 represents an alkyl group or an aryl group. and X represents halogen. ] by reacting the phosphorane represented by the general formula [ ] [In the formula, R 1 , R 3 and X have the same meanings as above. The compound of the present invention can be synthesized by a method in which a 5-(2-alkoxy or aryloxycarbonyl-2-halogenvinyl) uracil nucleoside represented by the formula is obtained and then hydrolyzed.
本法において、一般式〔〕化合物、すなわち
５−ホルミルウラシルヌクレオシドは公知化合物
であり、特にその調製法に制約がない。 In this method, the compound of general formula [], that is, 5-formyluracil nucleoside, is a known compound, and there are no particular restrictions on its preparation method.
また、第一の反応工程において反応試薬として
用いられるホスホランは前記一般式〔〕で表わ
されるが、その式中のR2のアルキル基および／
またはアリール基の具体例としてはメチル、エチ
ル、プロピル、ブチル、ベンジル、フエニル、ト
リルなどが挙げられる。三つのR2は互いに同一
である必要はなく、たとえば一つがメチルで他の
二つがフエニル、もしくは二つがエチルで一つが
トリルなどの場合を含む。R3のアルキル基また
はアリール基の具体例としてはメチル、エチル、
プロピル、ブチル、フエニルなどが挙げられる。
Ｘのハロゲンは臭素、塩素もしくはヨウ素であ
る。 In addition, the phosphorane used as a reaction reagent in the first reaction step is represented by the above general formula [], and in the formula, R 2 is an alkyl group and /
Specific examples of the aryl group include methyl, ethyl, propyl, butyl, benzyl, phenyl, and tolyl. The three R2s do not have to be the same, and include cases where one is methyl and the other two are phenyl, or two are ethyl and one is tolyl. Specific examples of the alkyl group or aryl group for R3 include methyl, ethyl,
Examples include propyl, butyl, phenyl, etc.
The halogen of X is bromine, chlorine or iodine.
第一工程の反応は反応溶媒中で行なわれる。反
応溶媒としては、たとえばジオキサン、テトラヒ
ドロフラン、エチレングリコールジメチルエーテ
ルなどのエーテル類、ジメチルホルムアミドなど
のアミド系溶媒、ジメチルスルホキシドなどを使
用しうる。反応条件にも特に制約はなく、室温条
件下で実施することができる。 The first step reaction is carried out in a reaction solvent. As the reaction solvent, for example, ethers such as dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether, amide solvents such as dimethylformamide, dimethyl sulfoxide, and the like can be used. There are no particular restrictions on the reaction conditions, and the reaction can be carried out at room temperature.
かくして得られる５−（２−アルコキシもしく
はアロキシカルボニル−２−ハロゲノビニル）体
の加水分解反応は、水酸化ナトリウム、水酸化カ
リウム、水酸化アンモニウム、炭酸ナトリウム、
炭酸水素ナトリウム、トリエチルアミンなどのア
ルカリを用いて水または含水溶媒（たとえば、ジ
オキサン−水、メタノール−水、エタノール−水
など）中で行う。反応は０℃〜室温で数時間の条
件下で実施することができる。 The hydrolysis reaction of the 5-(2-alkoxy or aryloxycarbonyl-2-halogenovinyl) body obtained in this way is carried out using sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium carbonate,
The reaction is carried out in water or a water-containing solvent (for example, dioxane-water, methanol-water, ethanol-water, etc.) using an alkali such as sodium hydrogen carbonate or triethylamine. The reaction can be carried out at 0°C to room temperature for several hours.
反応液からの本発明化合物の分離精製は常法に
よればよく、吸着カラムクロマトグラフイー、イ
オン交換カラムクロマトグラフイー、再結晶など
の方法を適宜に応用することができる。 The compound of the present invention may be separated and purified from the reaction solution by conventional methods, and methods such as adsorption column chromatography, ion exchange column chromatography, recrystallization, etc. can be applied as appropriate.
本発明化合物から５−（２−ハロゲノビニル）
ウラシルヌクレオシドを導くには、本発明化合物
を脱炭酸反応工程に付す。脱炭酸反応は塩基触媒
存在下で加熱反応させることにより行える。この
ような塩基触媒としては反応溶媒を兼ねてピリジ
ン、ピペリジン、ピロリジンなどの複素環塩基、
二級アミンを用いることができる。また反応を促
進させるために反応系にフツ素アニオンを存在さ
せることも有効である。反応温度は80℃〜溶媒還
流温度（たとえば115℃）の条件を設定すればよ
い。反応は15〜24時間で終了する。 5-(2-halogenovinyl) from the compound of the present invention
To derive uracil nucleoside, the compound of the present invention is subjected to a decarboxylation reaction step. The decarboxylation reaction can be carried out by heating the reaction in the presence of a base catalyst. Examples of such base catalysts include heterocyclic bases such as pyridine, piperidine, and pyrrolidine, which also serve as reaction solvents.
Secondary amines can be used. It is also effective to have a fluorine anion present in the reaction system in order to promote the reaction. The reaction temperature may be set from 80°C to the solvent reflux temperature (for example, 115°C). The reaction is complete in 15-24 hours.
以下、本発明化合物の製造例を実施例として示
し、また応用反応例を参考例として示して本発明
の実施態様のより具体的な説明とする。 Hereinafter, production examples of the compounds of the present invention will be shown as Examples, and applied reaction examples will be shown as Reference Examples to provide a more specific explanation of the embodiments of the present invention.
実施例 １
１−β−Ｄ−アラビノフラノシル−５−ホルミ
ルウラシル81.6mg、ブロモ（エトキシカルボニ
ル）メチレントリフエニルホスホラン141mgをジ
オキサン３mlに懸濁させ、室温にて４時間撹拌し
ながら反応させた。溶媒を留去した後、残渣をプ
レパラテイブ薄層クロマトグラフイー（PLC）
にて分離し（溶媒、クロロホルム−メタノール＝
10：１）、目的の部分をクロロホルム−メタノー
ル＝10：１で抽出し、溶媒を留去し、残渣をエタ
ノールから再結晶して１−β−Ｄ−アラビノフラ
ノシル−５−（２−ブロモ−２−エトキシカルボ
ニルビニル）ウラシル112mgを得た（収率89％）。Example 1 81.6 mg of 1-β-D-arabinofuranosyl-5-formyluracil and 141 mg of bromo(ethoxycarbonyl)methylenetriphenylphosphorane were suspended in 3 ml of dioxane and reacted with stirring at room temperature for 4 hours. Ta. After distilling off the solvent, the residue was subjected to preparative thin layer chromatography (PLC).
(solvent, chloroform-methanol =
10:1), the target portion was extracted with chloroform-methanol = 10:1, the solvent was distilled off, and the residue was recrystallized from ethanol to obtain 1-β-D-arabinofuranosyl-5-(2- 112 mg of bromo-2-ethoxycarbonylvinyl)uracil was obtained (yield: 89%).
融点 219〜220℃
紫外部吸収スペクトル
λEtOH nax 263nｍ、323nｍ
核磁気共鳴スペクトル（DMSO−d6）
ビニル基プロトン 8.17ppm
元素分析 C14H17N2Brとして
理論値 Ｃ、39.92；Ｈ、4.07；Ｎ、6.65；
Br、18.97
実測値 Ｃ、39.99；Ｈ、4.07；Ｎ、6.54；
Br、19.01
１−β−Ｄ−アラビノフラノシル−５−（２−
ブロモ−２−エトキシカルボニルビニル）ウラシ
ル121.4mgをジオキサン３mlに懸濁させ、0.5N水
酸化ナトリウム２mlを加えて室温で１時間撹拌し
ながら反応させた。強酸性カチオン交換樹脂ダウ
エツクス50W−X8（H+型）にてPH３〜４にし、
濾過後、溶媒を留去し、残渣を水より再結晶して
１−β−Ｄ−アラビノフラノシル−５−（２−ブ
ロモ−２−カルボキシビニル）ウラシル101mgを
得た（収率88％）。Melting point 219-220℃ Ultraviolet absorption spectrum λ EtOH nax 263 nm, 323 nm Nuclear magnetic resonance spectrum (DMSO-d 6 ) Vinyl group proton 8.17 ppm Elemental analysis C 14 H 17 N 2 Br as Br Theoretical value C, 39.92; H, 4.07; N, 6.65; Br, 18.97 Actual value C, 39.99; H, 4.07; N, 6.54; Br, 19.01 1-β-D-arabinofuranosyl-5-(2-
121.4 mg of bromo-2-ethoxycarbonylvinyl) uracil was suspended in 3 ml of dioxane, 2 ml of 0.5N sodium hydroxide was added, and the mixture was reacted with stirring at room temperature for 1 hour. Adjust the pH to 3 to 4 using the strongly acidic cation exchange resin Dowex 50W-X8 (H + type).
After filtration, the solvent was distilled off, and the residue was recrystallized from water to obtain 101 mg of 1-β-D-arabinofuranosyl-5-(2-bromo-2-carboxyvinyl)uracil (yield 88%). ).
融点 187℃（分解）
紫外部吸収スペクトル
λpH7 nax 261nｍ、308nｍ
元素分析 C12H13N2O8Brとして
理論値 Ｃ、36.66；Ｈ、3.33；Ｎ、7.13；
Br、20.32
実測値 Ｃ、36.48；Ｈ、3.32；Ｎ、7.02；
Br、20.16
応用例 １
１−β−Ｄ−アラビノフラノシル−５−（２−
ブロモ−２−カルボニルビニル）ウラシル40mgを
ピリジン２mlに溶解させ、80℃で18時間加熱反応
させ、さらに２時間100℃で加熱反応させた。溶
媒を留去した後、メタノールに溶解させ、PLC
（溶媒、クロロホルム：メタノール＝７：１）で
分離し、目的の部分をクロロホルム：メタノール
＝７：１で抽出し、溶媒を留去した後、水より再
結晶して１−β−Ｄ−アラビノフラノシル−５−
（２−ブロモビニル）ウラシルを得た。Melting point 187℃ (decomposition) Ultraviolet absorption spectrum λ pH7 nax 261nm, 308nm Elemental analysis C 12 H 13 N 2 O 8 As Br Theoretical value C, 36.66; H, 3.33; N, 7.13; Br, 20.32 Actual value C, 36.48 ; H, 3.32; N, 7.02; Br, 20.16 Application example 1 1-β-D-arabinofuranosyl-5-(2-
40 mg of bromo-2-carbonylvinyl) uracil was dissolved in 2 ml of pyridine, heated and reacted at 80°C for 18 hours, and further heated at 100°C for 2 hours. After distilling off the solvent, dissolve in methanol and perform PLC
(solvent, chloroform:methanol = 7:1), extract the target portion with chloroform:methanol = 7:1, distill off the solvent, recrystallize from water and 1-β-D-arabi. Nofuranosyl-5-
(2-bromovinyl)uracil was obtained.
融点 189℃（分解）
紫外部吸収スペクトル
λEtOH nax 253nｍ、295nｍ
核磁気共鳴スペクトル（DMSO−d6）ppm
7.16（ビニル基プロトン、Ｊ＝13Hz）
6.86（ビニル基プロトン、Ｊ＝13Hz）
7.89（Ｈ−６）
5.98（Ｈ−1′）
元素分析 C11H13N2O6Brとして
理論値 Ｃ、37.84；Ｈ、3.75；Ｎ、8.03；
Br、22.89
実測値 Ｃ、37.87；Ｈ、3.75；Ｎ、7.94；
Br、22.90
実施例 ２
１−β−Ｄ−2′−デオキシリボフラノシル−５
−ホルミルウラシル512mgをジメチルスルホキシ
ド５mlにブロモ（エトキシカルボニル）メチレン
トリフエニルホスホラン970mgを加え、撹拌下一
夜室温にて反応させた。溶媒を減圧下留去し、残
渣をプレパラテイブ薄層クロマトグラフイにて分
離し（溶媒、クロロホルム−メタノール＝20：
１）、目的の部分をクロロホルム−メタノール＝
10：１で抽出し、抽出液を濃縮乾固して１−β−
Ｄ−2′−デオキシリボフラノシル−５−（２−ブ
ロモ−２−エトキシカルボニルビニル）ウラシル
1.01ｇを得た。Melting point 189℃ (decomposition) Ultraviolet absorption spectrum λ EtOH nax 253nm, 295nm Nuclear magnetic resonance spectrum (DMSO-d 6 ) ppm 7.16 (vinyl group proton, J = 13Hz) 6.86 (vinyl group proton, J = 13Hz) 7.89 (H -6) 5.98 (H-1') Elemental analysis C 11 H 13 N 2 O 6 As Br Theoretical value C, 37.84; H, 3.75; N, 8.03; Br, 22.89 Actual value C, 37.87; H, 3.75; N , 7.94; Br, 22.90 Example 2 1-β-D-2′-deoxyribofuranosyl-5
- 512 mg of formyluracil and 970 mg of bromo(ethoxycarbonyl)methylenetriphenylphosphorane were added to 5 ml of dimethyl sulfoxide, and the mixture was reacted with stirring overnight at room temperature. The solvent was distilled off under reduced pressure, and the residue was separated by preparative thin layer chromatography (solvent: chloroform-methanol = 20:
1), convert the target part into chloroform-methanol=
Extract at a ratio of 10:1 and concentrate the extract to dryness to obtain 1-β-
D-2'-deoxyribofuranosyl-5-(2-bromo-2-ethoxycarbonylvinyl)uracil
1.01g was obtained.
核磁気共鳴スペクトル（DMSO−d6）δppm
9.00（Ｈ−６）
8.14（ビニル基プロトン）
１−β−Ｄ−2′−デオキシリボフラノシル−５
−（２−ブロモ−２−エトキシカルボニルビニル）
ウラシル634mgをジオキサン10mlに懸濁させ、
1.25M水酸化ナトリウム４mlを加え、室温にて撹
拌し、１〜２時間後、強酸性カチオン交換樹脂ダ
ウエツクス50W（H+型）でPH３とした後、樹脂を
濾去し、濾液を濃縮乾固して１−β−Ｄ−2′−デ
オキシリボフラノシル−５−（２−ブロモ−２−
カルボキシビニル）ウラシルを得た。Nuclear magnetic resonance spectrum (DMSO- d6 ) δppm 9.00 (H-6) 8.14 (vinyl group proton) 1-β-D-2'-deoxyribofuranosyl-5
-(2-bromo-2-ethoxycarbonylvinyl)
Suspend 634 mg of uracil in 10 ml of dioxane,
Add 4 ml of 1.25M sodium hydroxide, stir at room temperature, and after 1 to 2 hours, adjust the pH to 3 using a strongly acidic cation exchange resin Dowex 50W (H + type), remove the resin by filtration, and concentrate the filtrate to dryness. 1-β-D-2'-deoxyribofuranosyl-5-(2-bromo-2-
(carboxyvinyl) uracil was obtained.
核磁気共鳴スペクトル（DMSO−d6）δppm
8.68（Ｈ−６）
7.80（ビニル基プロトン）
6.24（Ｈ−1′）
応用例 ２
実施例２で得られた１−β−Ｄ−2′−デオキシ
リボフラノシル−５−（２−ブロモ−２−カルボ
キシビニル）ウラシルをピリジン10mlに溶解さ
せ、フツ化カリウム５mgを加え、20時間加熱還流
した。溶媒を留去し、残渣を薄層クロマトグラフ
イーにより分離して１−β−Ｄ−2′−デオキシリ
ボフラノシル−５−（２−ブロモビニル）ウラシ
ルを得た。Nuclear magnetic resonance spectrum (DMSO-d 6 ) δppm 8.68 (H-6) 7.80 (vinyl group proton) 6.24 (H-1') Application example 2 1-β-D-2'-deoxyribo obtained in Example 2 Furanosyl-5-(2-bromo-2-carboxyvinyl)uracil was dissolved in 10 ml of pyridine, 5 mg of potassium fluoride was added, and the mixture was heated under reflux for 20 hours. The solvent was distilled off and the residue was separated by thin layer chromatography to obtain 1-β-D-2'-deoxyribofuranosyl-5-(2-bromovinyl)uracil.
紫外線吸収スペクトル λnax 252nｍ、296nｍ 核磁気共鳴スペクトル（DMSO−d6）δppm 8.07（Ｈ−６） 7.25、6.81（Ｊ＝13Hz、ビニル基プロトン） 6.12（Ｈ−1′）Ultraviolet absorption spectrum λ nax 252 nm, 296 nm Nuclear magnetic resonance spectrum (DMSO-d 6 ) δppm 8.07 (H-6) 7.25, 6.81 (J = 13 Hz, vinyl group proton) 6.12 (H-1')
Claims (1)
ロゲンを示す。〕で表わされる５−（２−カルボキ
シ−２−ハロゲノビニル）ウラシルヌクレオシ
ド。[Claims] 1. General formula [] [In the formula, R 1 represents hydrogen or a hydroxyl group, and X represents a halogen. ] 5-(2-carboxy-2-halogenovinyl)uracil nucleoside.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3795583A JPS59163395A (en) | 1983-03-08 | 1983-03-08 | 5-(2-carboxy-2-halogenovinyl)uracil nucleoside |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3795583A JPS59163395A (en) | 1983-03-08 | 1983-03-08 | 5-(2-carboxy-2-halogenovinyl)uracil nucleoside |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59163395A JPS59163395A (en) | 1984-09-14 |
| JPH027592B2 true JPH027592B2 (en) | 1990-02-19 |
Family
ID=12511970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3795583A Granted JPS59163395A (en) | 1983-03-08 | 1983-03-08 | 5-(2-carboxy-2-halogenovinyl)uracil nucleoside |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59163395A (en) |
-
1983
- 1983-03-08 JP JP3795583A patent/JPS59163395A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59163395A (en) | 1984-09-14 |
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