抗糖尿病药物瑞格列奈的合成

抗糖尿病药物瑞格列奈的合成

赵爽¹, 徐志炳¹, 鄂晨光¹, 李卓¹, 王恩思¹,²

1. 吉林大学生命科学学院, 长春 130021； 2. 吉林大学药学院, 长春 130021

收稿日期:2007-06-28 修回日期:1900-01-01 出版日期:2008-05-26 发布日期:2008-05-26
通讯作者: 王恩思

Synthesis of Antidiabetic Medicine Repaglinide

ZHAO Shuang¹, XU Zhibing¹, E Chenguang¹, LI Zhuo¹, WANG Ensi¹,²

1. College of Life Science, Jilin University, Changchun 130021, China; 2. College of Pharmacy, Jilin University, Changchun 130021, China

Received:2007-06-28 Revised:1900-01-01 Online:2008-05-26 Published:2008-05-26
Contact: WANG Ensi

摘要/Abstract

摘要： 以4-甲基水杨酸、 2-氯苯腈为原料, 采用LDA/DMPU 催化羧基化和Ph3P催化缩合反应为关键步骤合成瑞格列奈, 总收率为10.5%. 该合成方法具有工艺路线短、总收率高、操作简单等优点, 适合工业化生产. 其中关键中间体及瑞格列奈的结构用元素分析、红外光谱、核磁共振氢谱及碳谱、质谱和比旋光等方法表征.

关键词: 瑞格列奈, 化学拆分, 旋光性, 抗糖尿病药物

Abstract: Repaglinide (a new antidiabetic medicine), (S)(+)-2-ethoxy-4-［N-［1-(2-piperidinophenyl)-3-methyl-1-butyl］aminocarbo nylmethyl］benzoic acid, was synthesized by means of Ph3P catalyzed condensation and LDA/DMPU catalyzed carboxylation as pivotal steps from the starting materials 4-methylsalicylic acid and 2-chlorobenzonitrile. Repaglinide was synthesized in a total yield of 10.5%. The structures of the targetmolecule and the key intermediates were confirmed by IR, ¹H NMR,¹³C NMR, elemental analysis, specific rotation and MS techniques.

Key words: repaglinide, chemical resolution technique, optical r otation, antidiabetic medicine

中图分类号:

R977.15

赵爽, 徐志炳, 鄂晨光, 李卓, 王恩思,. 抗糖尿病药物瑞格列奈的合成[J]. J4, 2008, 46(03): 556-559.

ZHAO Shuang, XU Zhibing, E Chenguang, LI Zhuo, WANG Ensi,. Synthesis of Antidiabetic Medicine Repaglinide[J]. J4, 2008, 46(03): 556-559.

[1]	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.
[2]	尹建元,王恩思. 口服降糖药曲格列酮的核磁共振谱学表征[J]. J4, 2002, 40(04): 423-425.