顺式那格列奈的合成

Synthesis of Cis- Nateglinide

首次报道了抗糖尿病新药那格列奈异构体-顺式那格列奈的合成方法。实验中将4-异丙基苯甲酸溶于醋酸中,在催化剂作用下氢化得4-异丙基环己甲酸的顺反异构体混合物,经过硫脲及N-羟基琥珀酰亚胺处理而得顺式4-异丙基环己甲酸琥珀酯,再与D-苯丙氨酸甲酯盐酸盐反应,然后于碱性条件下水解得到顺式那格列奈.以起始原料4-异丙基苯甲酸计,顺式顺式那格列奈纯度为98.8%,总收率为7.63%。

The preparation of a new antidiabetic drug cis-isomer nateglinide was first time described. In experiments ,4-isopropylbenzoate was dissolved in acetic acid ,which washydrogenated by catalyzers PtO_ 2 and the results were the mixture of 4-isopropylcyclohexane carboxylic acid. By treatment above mixture with thiourea and N-Hydroxysuccinimide, Cis-4-isopropylcyclohexane amboryl formate was obtained and them reacted with D-Phenylalanine methyl esterhydrochloride andhydrolyzed on basic. Finally , cis-nateglinide was obtained. The total yields is 7.63% according to the initial material 4-isopropylbenzoate and the purity is 98.8%.