催化学报

催化学报 ›› 2010, Vol. 31 ›› Issue (6): 651-655.

• 研究论文 • 上一篇    下一篇

脂肪酶 Novozyme 435 选择性催化2,2-二甲基环丙烷甲酸乙酯合成S-(+)-2,2-二甲基环丙烷甲酸

王普, 祝加男, 何军邀   

  1. 浙江工业大学药学院, 浙江杭州 310032
  • 收稿日期:2010-06-25 出版日期:2010-06-25 发布日期:2013-12-05

Enantioselective Synthesis of S-(+)-2,2-Dimethylcyclopropanecarboxylic Acid from Ethyl-2,2-dimethylcyclopropanecarboxylate Catalyzed by Lipase Novozyme 435

WANG Pu*, ZHU Jianan, HE Junyao   

  1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, Zhejiang, China
  • Received:2010-06-25 Online:2010-06-25 Published:2013-12-05

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1691

被引次数

23

摘要： 采用脂肪酶催化外消旋 2,2-二甲基环丙烷甲酸乙酯 (DMCPE) 不对称水解合成西司他丁关键手性中间体 S-(+)-2,2-二甲基环丙烷甲酸 (S-(+)-DMCPA). 比较了 5 种不同来源的脂肪酶, 从中优选出立体选择性较高和催化活性较高的脂肪酶 Novozyme 435, 系统考察了影响该酶催化不对称水解反应的关键因素, 获得了优化的生物催化工艺条件. 结果表明, 当脂肪酶 Novozyme 435 用量为 16 g/L, 底物 DMCPE 浓度为 65 mmol/L 时, 以 pH 值为 7.2 的磷酸缓冲液 (1 mol/L) 为反应介质, 30 oC 反应 64 h, 产物的收率和光学纯度分别为 45.6% 和 99.2%. 脂肪酶 Novozyme 435 催化 DMCPE 不对称水解制备 S-(+)-DMCPA 工艺的产物光学纯度高, 路线可行, 并且酶可重复使用, 具有良好的工业化应用前景.

关键词: 脂肪酶, 2-二甲基环丙烷甲酸乙酯, 不对称水解, S-(+)-2, 2-二甲基环丙烷甲酸, 手性中间体

Abstract: S-(+)-2,2-dimethylcyclopropanecarboxylic acid (S-(+)-DMCPA) was synthesized by asymmetric hydrolysis of racemic ethyl-2,2- dimethylcyclopropane carboxylate (DMCPE) over different lipases. Among the five enzymes investigated, Novozyme 435 showed higher enantioselectivity and activity. The influence of reaction parameters, such as ionic strength, the ratio of lipase/DMCPE, buffer pH, reaction temperature, and reaction time, on the biosynthesis of S-(+)-DMCPA was investigated. The optimum DMCPE concentration, enzyme dosage, buffer pH, reaction temperature, and reaction time were 65 mmol/L, 16 g/L, 7.2, 30 oC, and 64 h, respectively. Under the optimal conditions, the higher yield of 45.6% and enantiomeric excess of 99.2% for S-(+)-DMCPA were obtained. The biocatalytic activity of Novozyme 435 was relatively stable, retaining 70.3% of the initial activity after reuse three times. The results demonstrated that lipase Novozyme 435 is a suitable biocatalyst for the synthesis of S-(+)-DMCPA and has great potential for industrial applications.

Key words: lipase, ethyl-2, 2-dimethylcyclopropanecarboxylate, asymmetric hydrolysis, S-(+)-2, 2-dimethylcyclopropanecarboxylic acid, chiral intermediate