Efficient synthesis of terminal α,β-unsaturated ketones as the intermediates of the proteasome epoxyketone inhibitors via Weinreb amide  

由Weinreb酰胺有效合成环氧酮类蛋白酶体抑制剂的中间体:末端α,β-不饱和酮(英文)

作　　者：吕杨[1] 邹晓民[1] 牟科[1] 傅翌秋[1] 马超[1] 周博[1] 徐萍[1] 

机构地区：[1]北京大学药学院药物化学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2009年第1期33-36,共4页中国药学（英文版）

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

摘　　要：Peptidyl epoxyketones were potential antitumor agents due to their 20S proteasome inhibitory activities. Based on their structures and special inhibitory mechanism, a series of compounds were designed by linking the epoxyketone moiety （the Cterminal pharmacophore） and the peptide backbones. To make these compounds, we used a novel method to prepare the terminal α,β-unsaturated ketone, the crucial intermediate, from Weinreb amide with satisfactory yield （62%-65%）.肽基环氧酮类化合物对20S蛋白酶体具有抑制作用, 使之成为可能的抗肿瘤药物。根据此类抑制剂的结构和特殊抑制机理,我们设计了一系列连接环氧酮部分(C-末端药效团) 和肽骨架的化合物。合成工作方面, 我们使用了经过Weinreb酰胺得到关键中间体末端α,β-不饱和酮的新合成方法, 产率为62%-65%。

关 键 词：Epoxyketone SYNTHESIS α β-Unsaturated ketone Weinreb amide 

分 类 号：R914[医药卫生—药物化学]