新型抗糖尿病药物那格列奈的化学酶促合成

Chemoenzymic synthesis of a new class of oral hypoglycemic agent nateglinide

以 4 异丙基苯甲醇为原料 ,对治疗Ⅱ型糖尿病新药那格列奈进行化学 酶促合成。采用两种不同的路线合成那格列奈 ,总收率分别为 18%和 2 9%。实验表明 :经由酶法水解反应的途径具有收率较高、反应条件温和等特点 ,关键中间体及最终化合物的结构经元素分析、质谱、核磁共振氢谱及碳谱得到确证。

Aim To chemoenzymically synthesize nateglinide (a new kind of hypoglycemic drugs which may play a role in the treatment of the type 2 diabete mellitus).Method Nateglinide, N [( trans 4 isopropylcyclohexyl) carbonyl] D phenylalanine was synthesized by the two different synthetic routes from 4 isopropylbenzoic acid as the starting material.Results The total yields were 18% and 29%,respectively.The structures of the intermediates and target molecules were confirmed by MS,elementary analysis, 1H NMR and 13 C NMR spectra in the experiments.Conclusion The route via the enzymic hydrolysis was convenient and simple.The route without a high temperature may be applied to the industrial production.