那格列奈合成方法研究

Study on Synthesis of Nateglinide

目的研究那格列奈的合成新方法。方法β-蒎烯经氧化得到诺蒎酸,诺蒎酸开四元环得到二氢枯茗酸,再经过催化加氢、异构得到反-4-异丙基环己烷甲酸,反-4-异丙基环己烷甲酸转变成酰氯后和D-苯丙氨酸反应得到N-(反-4-异丙基环己烷羰基)-D-苯丙氨酸,即2型糖尿病新药那格列奈的原料药。结果那格列奈及反-4-异丙基环己烷甲酸经红外、核磁、质谱证实。结论本法采用天然原料,反应条件温和,操作简单,总收率高。

OBJECTIVE To study the new synthesis of nateglinide. METHODS β-Pinene was oxidated with KMnO4 in the presence of pyridine to yield nopinic acid, then acid-catalyzed ring opened to yield dihydrocumic acid, which was hydrogenated with Pd/ C and epimerizated to yield trans-4-isopropylhexanecarboxylic acid. Trans- 4-isopropylhexanecarboxylic acid was changed to its acryl chloride with PCl5 , reacted with D-phenylalanine to yield the title compound nateglinide. RESULTS The structures of nateglinide and trans-4-isopropylhexane carboxylic acid were identified by IR, NMR and MS. CONCLUSION This method uses the natural product β-pinene as the material,and the reaction conditions are facile and simple in all steps.