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

作     者：吕杨 邹晓民 牟科 傅翌秋 马超 周博 徐萍 

作者机构：北京大学药学院药物化学系北京100191 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2009年第18卷第1期

页      面：33-36页

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

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

主　　题：Epoxyketone Synthesis α,β-Unsaturated ketone Weinreb amide 

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%）.