Synthesis of acyclic analogs of Syringolin A as potential 20S proteasome inhibitors  

20S蛋白酶体抑制剂Syringolin A开环类似物的合成(英文)

作　　者：袁悦[1] 邹晓民[1] 牛彦[1] 许凤荣[1] 牟科[1] 周博[1] 王超[1] 李勇剑[1] 杨冠宇[1] 徐萍[1] 

机构地区：[1]北京大学医学部药学院药物化学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2010年第6期423-435,共13页中国药学（英文版）

基　　金：National Natural Science Foundation of China (Grant No.20772008 and 30772650)

摘　　要：A series of acyclic analogs of natural product Syringolin A （SylA） were designed and synthesized during our synthetic efforts for SylA. These acyclic analogs were prepared through a seven-step linear strategy, with total yields varying from 20%-34% for one type of analogs and 12%-18% for the other. These compounds bear a common structure of peptidyl vinyl amide, which reacts irreversibly with the proteasomal active site ThrlO^γ through Michael-type 1,4-addition. Therefore, these acyclic analogs may function the same way as SylA, as potential 20S proteasome inhibitors.本文报道了在合成天然的蛋白酶体抑制剂symgolinA（SylA）及其类似物的过程中，首先合成的两种类型的SylA开环类似物。经过7步反应，第一种类型产物总收率在20％-34％之间，第二种类型产物总收率在12％-18％之间。与SylA相似，这两种类型的类似物也都具有肽乙烯酰胺的结构，可能作为Michael受体与蛋白酶体催化活性位点ThrlO^γ发生1,4-加成反应，从而发挥蛋白酶体抑制活性。

关 键 词：Syringolin A 20S proteasome Peptidyl vinyl amide 

分 类 号：R914[医药卫生—药物化学]