新型降糖候选化合物ZG02的合成方法改进及其手性分离

Improvement on Synthesis of Novel Hypoglycemic Candidate ZG02 and Chiral Separation

研究发现新型四氢咔唑衍生物ZG02有较强的体内外降糖与降脂活性,是一个有深入开发价值的候选化合物。前期报道的制备方法存在总产率低、纯化困难等问题。本研究经方法改进后以4-氧代环己基甲酸为原料,经烯丙基保护、Fischer-吲哚环合、酰化及脱保护等4步反应得到目标产物,总收率为71.9%。同时,利用手性制备柱对ZG02进行了拆分,得到了光学纯异构体,以便进一步评价不同构型异构体的生物活性差异。

The work revealed that novel tetrahydrocarbazole derivative ZG02 possessed potent hypoglycemic and hypolipemic activities both in vitro and in vivo and thus,a promising candidate for the treatment of type 2 diabetes. The previous method suffered from low total yield and hard for purification. In this work,taking 4-oxocyclohexanecarboxylic acid as starting material,the title compound was synthesized via allylation,Fischer indole synthesis,acylation and deprotection with a total yield of 71. 9%.Besides,a chiral separation on ZG02 and optically pure isomers were obtained via preparative column,and therefore provide samples for further bio-evaluations.