ZSP0678的合成工艺研究

Study on the synthetic process of ZSP0678

目的优化PPARα/δ双重激动剂ZSP0678的合成工艺。方法以(E)-2-{2,6-二甲基-4-[4-(4-甲硫基苯基)-4-氧代-2-丁烯-1-基]苯氧基}-2-甲基丙酸乙酯(2)为起始原料,经环化、水解、手性拆分、酰胺化反应得到ZSP0678。结果目标化合物的结构经1H-NMR、13C-NMR和ESI-MS谱确证,总收率为6.5%(以化合物2计),化学纯度为98.6%(HPLC),光学纯度为99.2%。结论该工艺操作简便,避免使用柱色谱分离提纯,提高了总收率,有利于ZSP0678的大量制备。

ZSP0678 is a PPARα/δdual agonists.Herein,the synthetic process of ZSP0678 was studied.The ZSP0678 was synthesized via cyclization,hydrolysis,chiral separation and amidation reaction using ethyl(E)-2-(2,6-dimethyl-4-(4-(4-(methylthio)phenyl)-4-oxobut-2-en-1-yl)phenoxy)-2-methylpropanoate as the starting material.The structures of ZSP0678 was identified by~1H-NMR,13C-NMR and ESI-MS.The purity of the target compound was 98.6%(HPLC),and the chiral purity was 99.2%.The improved process has several advantages,such as simple operation,easy separation and purification and higher yield,and was suitable for large scale preparation.