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有机化学 ›› 2007, Vol. 27 ›› Issue (05): 678-681. 上一篇    下一篇

研究简报

(S)-和(R)-普萘洛尔的不对称合成

王燕，沈大冬，朱锦桃*   

  1. (浙江理工大学化学系 杭州 310018)
  • 收稿日期:2006-06-20 修回日期:2006-09-28 发布日期:2007-05-10
  • 通讯作者: 朱锦桃*

Asymmetric Synthesis of S- and R-Propranolols

WANG Yan, SHEN Da-Dong, ZHU Jin-Tao*   

  1. (Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018)
  • Received:2006-06-20 Revised:2006-09-28 Published:2007-05-10
  • Contact: ZHU Jin-Tao

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普萘洛尔是一种临床上广泛使用的β受体阻断剂, 介绍了一种不对称合成(S)-和(R)-普萘洛尔的方法. 以手性Salen-CoIII催化剂水解动力学拆分外消旋环氧氯丙烷得到高光学纯度的(S)-环氧氯丙烷和(R)-3-氯-1,2-丙二醇, 以(S)-环氧氯丙烷为手性原料先水解得(S)-3-氯-1,2-丙二醇, 其与1-萘酚反应得(S)-3-(1-萘基)-丙烷-1,2-二醇, 再与氯化亚砜反应得环状亚硫酸酯, 最后和异丙胺作用得(S)-普萘洛尔, 总收率80.9%, 光学纯度大于99%; 而同样以(S)-环氧氯丙烷为手性原料直接与1-萘酚反应得(2R)-3-(1-萘氧基)-1,2-环氧丙烷, 再与异丙胺作用得(R)-普萘洛尔, 总收率74.5%, 光学纯度大于99%.

关键词: (R)-普萘洛尔, (S)-环氧氯丙烷, 不对称合成, I>S)-普萘洛尔

The asymmetric synthesis of propranolol, β-blocker inhibitor, was described. Highly enantioenriched (S)-epichlorohydrin and (R)-3-chloro-1,2-propanediol were obtained from the kinetic hy-drolysis resolution of racemic epichlorohydrin by chiral salen-CoIII complex. (S)-Epichlorohydrin was used as chiral reagent to synthesize (S)- and (R)- propranolols in yields of 80.9% and 74.5% with. higher than 99% ee.

Key words: (R)-propranolol, (S)-epichlorohydrin, asymmetric synthesis<, S)-propranolol