奈必洛尔中间体的不对称合成  

Asymmetric Synthesis of Nebivolol Intermediates

作　　者：张青山[1] 黄小光[1] 李爱英[1] 

机构地区：[1]北京理工大学化工与环境学院,北京100081

出　　处：《北京理工大学学报》2005年第6期546-550,共5页Transactions of Beijing Institute of Technology

基　　金：教育部留学回国人员科研启动基金资助项目(367-4)

摘　　要：(S,R,R,R)-奈必洛尔是一种新型、强效的β1-肾上腺素能受体阻滞剂降压药物.采用氧化/Wittig烯化一锅煮反应和Sharpless不对称环氧化/环化一锅煮反应,经八步反应,不对称合成出(S,R,R,R)-奈必洛尔的两个关键中间体1-[6-氟-(2S)-3,4-二氢-2H-2-苯并吡喃]-(1R)-1,2-乙二醇和1-[6-氟-(2R)-3,4-二氢-2H-2-苯并吡喃]-(1S)-1,2-乙二醇.该合成路线工艺简单,单步反应产率高,八步反应总收率达19%.<Abstrcat> (S, R, R, R)-nebivolol is a novel and effective β_1-adrenergic antagonist with antihypertensive activity. The oxidation/Wittig olefination 'one-pot' and the Sharpless asymmetric epoxidation/cyclization 'one-pot' are adopted in this route of synthesis. 1-[6-fluoro-(2S)-3,4-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol and 1-[6-fluoro-(2R)-3,4-dihydro-2H-2-chromenyl]-(1S)-1,2-ethanediol, the two key intermediates of nebivolol, are obtained in eight steps by the asymmetric synthesis route. The synthesis protocol is convenient and each step has a high yield, thus the overall yield can reach 19%.

关 键 词：奈必洛尔 氧化/Wittig烯化 Sharpless不对称环氧化/环化 

分 类 号：O621.256[理学—有机化学]