那格列奈的合成  

Synthesis of nateglinide

作　　者：安林坤[1] 郭新东[1] 宋晓虹[2] 黄仲立[3] 卜宪章[1] 黄志纾[1] 古练权[1] 

机构地区：[1]中山大学药学院,广州510080 [2]中山大学生命科学院,广州510080 [3]中山大学 测试中心,广州510080

出　　处：《中国新药杂志》2006年第18期1564-1566,共3页Chinese Journal of New Drugs

基　　金：广东省自然科学基金(4300235)

摘　　要：目的:合成抗2型糖尿病药物那格列奈。方法:以对异丙基苯甲醛为原料,经氧化、催化氢化、在高温高压碱性条件下,将顺式-对异丙基环已甲酸异构化为反武．异构体,然后与D-苯丙氨酸甲酯盐酸盐缩合、水解,合成那格列奈。结果:反应中间体以及目标产物的化学结构均经过了光谱分析确证,反应总收率为28．7％。结论:本方法步骤简单,易于工业化生产。Objective：To synthesize nateglinide, an anti-type 2 diabetic agent. Methods： Starting from 4-isopropylbenzaldehyde, trans-4-isopropylcyclohexanecarboxylic acid was isomerized to cis-isomer via oxidation, catalytic hydrogenation and then high temperature and high pressure in alkali aqueous. Nateglinide was synthesized after the cis-isomer was reacted with D-phenylalanine and hydrolysis. Results： The structures of intermediates and the target product were verified by spectroscopic analysis. The overall yield was 28.7%. Conclusion： The simplified method to synthesize nateglinide was warranted to have further pilot manufacture.

关 键 词：那格列奈 2型糖尿病 药物合成 

分 类 号：R977.15[医药卫生—药品] R914.5[医药卫生—药学]