γ-丁内酯类衍生物的合成及其脂肪酸合成酶抑制活性的研究

Synthesis of γ-butyrolactone derivatives as FAS inhibitors

目的以C75为先导化合物,设计、合成γ-丁内酯类衍生物,并研究其脂肪酸合成酶(fatty acid syn-thase,FAS)的抑制活性,以期发现新颖的FAS抑制剂。方法以衣康酸酐为起始原料,经酯化、烃代、缩合/环合、水解4步反应合成目标化合物,采用体外方法初步筛选其FAS的抑制作用。结果与结论合成了11个目标化合物,其结构经核磁和质谱确证;初步活性评价结果显示,含饱和烷烃侧链的化合物具有较好的FAS抑制活性,随侧链烷基的延长,其抑酶活性有增强的趋势。

Aim To design and synthesize a series of novel γ-butyrolactone derivatives with FAS（fatty acid synthase,FAS） inhibition activities,C75 as the lead compound.Methods The target compounds were synthesized from itaconic anhydride through a four-step process.The FAS inhibition activities were tested in vitro.Results and conclusion Eleven new compounds were synthesized,and their structures were confirmed by FAB-MS and 1H-NMR.The preliminary pharmacological testing results showed that ME-11、ME-12 and ME-13 have almost equal FAS inhibition activities to that of C75.