- 著者
- 末宗 洋 田中 正一 尾葉石 浩 酒井 浄
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.36, no.1, pp.15-21, 1988-01-25 (Released:2008-03-31)
- 参考文献数
- 9
- 被引用文献数
- 9 18
Synthesis of prostaglandin A2 (PGA2) by means of a route involving enzymatic reactions is described. Enantioselective reduction and hydrolysis of trans-3, 4-bis(methoxycarbonyl)cyclopentanone (1) were examined using yeasts or enzymes, and it was found that (+)- and (-)-1 are easily obtained by an enzymatic procedure. Compound (+)-1 was converted to the Corey intermediate for PGA2 via the regioselective hydrolysis of the (+)-diacetate (8) with porcine pancreatic lipase. This synthesis based on the enzymatic approach was proved to be useful for the synthesis of both PGA and PGE from (-)-1.
- 著者
- 宮澤 修平 岡野 和夫 下村 直之 / 川原 哲也 浅野 修 吉村 寛幸 宮本 光明 佐久間 義範 村本 賢三 尾葉石 浩 原田 耕吉 梶間 隆 山田 浩司 角田 創 片山 敏 阿部 信也 浅川 直樹 左右田 茂 堀江 透 里 忠 町田 善正 片山 幸一 山津 功 Isao YAMATSU
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.39, no.12, pp.3215-3220, 1991-12-25 (Released:2008-03-31)
- 参考文献数
- 27
- 被引用文献数
- 6 9
A series of triazolodiazepines was synthesized and evaluated for anti-platelet activating factor (PAF) activities. Structure-activity relationship (SAR) studies on this series revealed that the introduction of a methyl group into the 8-position of the thienodiazepine nucleus can lead to a lengthening of the duration of action. Introduction of a methyl group produced an asymmetric center and the enantiomers so formed were separated with an optical resolving column. In the in vitro assay system, the (+)-isomers displayed 50-200 times more potent anti-PAF activity than the (-)-isomers. After comparison of toxicology and pharmacokinetics, (+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8, 11-dimethyl-2, 3, 4, 5-tetrahydro-8H-pyrido[4', 3' : 4, 5]thieno[3, 2-f][1, 2, 4]triazolo[4, 3-a][1, 4]diazepine (35(+)-isomer, E6123) was selected from among the compounds synthesized as a candidate for clinical study.