20S蛋白酶体抑制剂Syringolin A开环类似物的合成

doi:10.5246/jcps.2010.06.057

20S蛋白酶体抑制剂Syringolin A开环类似物的合成

袁悦, 邹晓民, 牛彦, 许凤荣, 牟科, 周博, 王超, 李勇剑, 杨冠宇, 徐萍^*

北京大学医学部药学院药物化学系, 北京 100191

收稿日期:2010-05-25 修回日期:2010-10-15 出版日期:2010-11-30 发布日期:2010-11-30
通讯作者: 徐萍*

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

Yue Yuan, Xiao-Min Zou, Yan Niu, Feng-Rong Xu, Ke Mou, Bo Zhou, Chao Wang, Yong-Jian Li, Guan-Yu Yang, Ping Xu^*

Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2010-05-25 Revised:2010-10-15 Online:2010-11-30 Published:2010-11-30
Contact: Ping Xu*

摘要/Abstract

摘要：

本文报道了在合成天然的蛋白酶体抑制剂Syringolin A (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Thr1O^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蛋白酶体, 肽乙烯酰胺

Abstract:

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 Thr1O^γ through Michael-type 1,4-addition. Therefore, these acyclic analogs may function the same way as SylA, as potential 20S proteasome inhibitors.

Key words: Syringolin A, 20S proteasome, Peptidyl vinyl amide

中图分类号:

R916.4

Supporting: Foundation items: National Natural Science Foundation of China (Grant No. 20772008 and 30772650).
^*Corresponding author. Tel.: 86-10-82801505

袁悦, 邹晓民, 牛彦, 许凤荣, 牟科, 周博, 王超, 李勇剑, 杨冠宇, 徐萍^*. 20S蛋白酶体抑制剂Syringolin A开环类似物的合成[J]. , DOI: 10.5246/jcps.2010.06.057.

Yue Yuan, Xiao-Min Zou, Yan Niu, Feng-Rong Xu, Ke Mou, Bo Zhou, Chao Wang, Yong-Jian Li, Guan-Yu Yang, Ping Xu^*. Synthesis of acyclic analogs of Syringolin A as potential 20S proteasome
inhibitors [J]. , DOI: 10.5246/jcps.2010.06.057.

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