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有机化学
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有机化学 ›› 2009, Vol. 29 ›› Issue (12): 1997-1999. 上一篇    下一篇

研究简报

(R)-4-氰基-3-羟基丁酸乙酯的合成

吕世翔a；郭阳辉b；王亚平b；王相晶a；向文胜*,a   

  1. (a东北农业大学生物化工系 哈尔滨 150030) 
    (b浙江海正药业股份有限公司 台州 318000)
  • 收稿日期:2009-02-16 修回日期:2009-06-05 发布日期:2009-07-08
  • 通讯作者: 向文胜 E-mail:13857680603
  • 基金资助:

    国家支撑计划(No. 2006BAD31B02)；黑龙江省杰出青年基金(No. JC200706)资助项目

Synthesis of (R)-4-cyano-3-hydroxybutyric acid ethyl ester

Lü, Shixianga；Guo, Yanghuib；Wang, Yapingb；Wang, Xiangjinga；Xiang, Wensheng*,a   

  1. (a Department of Biochemical Engineering, Northeast Agricultural University, Harbin 150030) (b Zhejiang Hisun Pharmaceutical Co., Ltd, Taizhou 318000)
  • Received:2009-02-16 Revised:2009-06-05 Published:2009-07-08

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研究了一条新的路线用于他汀类药物的重要中间体(R)-4-氰基-3-羟基丁酸乙酯的合成. 以廉价、易得的L-(－)-苹果酸为起始原料, 经酯化、还原、溴代和氰化四步反应得到目标化合物(R)-4-氰基-3-羟基丁酸乙酯, 合成总收率为56.7%. 所有中间体和最终产物均由ESI-MS, 1H NMR和13C NMR光谱及比旋光度表征并与文献值比较. 该方法原料易得、操作简便、收率良好, 产物容易分离纯化, 是一条适合大规模制备(R)-4-氰基-3-羟基丁酸乙酯的新合成工艺路线.

关键词: (R)-4-氰基-3-羟基丁酸乙酯, L-(－)-苹果酸, (3S)-3,4-二羟基丁酸乙酯, (S)-4-溴-3-羟基丁酸乙酯, 合成

A novel method for synthesis of (R)-4-cyano-3-hydroxybutyric acid ethyl ester (1), a key intermediate of statins, was reported. The target compound 1 was successfully prepared via esterification, reduction, bromization and cyanation processes by using L-(—)-malic acid (2), which is an inexpensive and easily available starting material. The overall yield was 56.7%. The structures of intermediates and final product were determined by ESI-MS, 1H NMR, 13C NMR techniques, optical rotation and comparison with reported data. This method with the advantages of simply available starting material, easily conducted procedure, relatively high yield and easy purification is more suitable for scale-up production.

Key words: (R)-4-cyano-3-hydroxybutyric acid ethyl ester, L-(—)-malic acid, (3S)-3,4-dihydroxybutyric acid ethyl ester, (S)-4-bromo-3-hydroxybutyric acid ester, synthesis