通过酶促拆分制备S(+)3-甲基-1-(2-（1-哌啶基）苯基)丁胺

J4 ›› 2010, Vol. 48 ›› Issue (06): 1043-1046.

通过酶促拆分制备S(+)3-甲基-1-(2-（1-哌啶基）苯基)丁胺

赵爽¹, 杨丽娟², 吴佳桢¹, 林凡³, 房学迅^1,4, 王恩思^1,2

1. 吉林大学生命科学学院, 长春 130012； 2. 吉林大学药学院, 长春 130021；3. 东北师范大学生命科学学院, 长春 130024； 4. 吉林大学分子酶学工程教育部重点实验室, 长春 130012

收稿日期:2010-03-04 出版日期:2010-11-26 发布日期:2010-11-26
通讯作者: 房学迅 E-mail:fangxx@jlu.edu.cn

Preparation of S(+)3-Methyl-1-(2-(1-piperidinyl)phenyl)butylamine through Enzymatic Catalysis

ZHAO Shuang¹, YANG Lijuan², WU Jiazhen¹, LIN Fan³, FANG Xuexun^1,4, WANG Ensi^1,2

1. College of Life Science, Jilin University, Changchun 130012, China;2. College of Phamacy, Jilin University, Changchun 130021, China;3. School of Life Science, Northeast Normal University, Changchun 130024, China;4. Key Laboratory for Molecular Enzymology and |Engineering, |the Ministry of Education, Jilin University, Changchun 130012, China

Received:2010-03-04 Online:2010-11-26 Published:2010-11-26
Contact: FANG Xuexun E-mail:fangxx@jlu.edu.cn

摘要/Abstract

摘要：

以脂肪酶Novozym435为催化剂, 乙酸乙酯作溶剂和酰基供体, 酶促合成瑞格列奈关键中间体S(+)3-甲基-1-(2-（1-哌啶基）苯基)丁胺, 总收率为17%. 该酶促拆分方法较化学拆分法具有高度的对映选择性及底物的专一性, 副反应少, 反应条件温和, 合成路线易于操作, 酶经活化后可重复利用.

关键词: 酶促合成；瑞格列奈中间体；脂肪酶Novozym435；药物化学

Abstract:

With lipase Novozym435 as catalyst, ethyl acetate as solvent as well as acyl donor, the crucial intermediatesS(+)3-methyl-1-(2-(1-piperidinyl)phenyl) butylamine of Repaglinide was synthesized enzymatically with a total yield of 17%. Compared with chemical catalysts, the enzymatic resolution method has higher enantioselectivity, regioselectivity and substrate specificity. The synthetic route is easy to operate under a moderate condition with less secondary reaction. Enzyme can be reutilized after activation, which reduces cost, and thus applied to industrial production.

Key words: synthesis promoted by enzyme, Repaglinide intermediate, lipase Novozym435, pharmaceutical chemistry

中图分类号:

R977.15

赵爽, 杨丽娟, 吴佳桢, 林凡, 房学迅, 王恩思. 通过酶促拆分制备S(+)3-甲基-1-(2-（1-哌啶基）苯基)丁胺[J]. J4, 2010, 48(06): 1043-1046.

DIAO Shuang, YANG Li-Juan, TUN Jia-Zhen, LIN Fan, FANG Hua-Xun, WANG En-Sai. Preparation of S(+)3-Methyl-1-(2-(1-piperidinyl)phenyl)butylamine through Enzymatic Catalysis[J]. J4, 2010, 48(06): 1043-1046.