A highly efficient way to recycle inactive stereoisomers of Bedaquiline into two previous intermediates via base-catalyzed C_(sp3)–C_(sp3) bond cleavage

作     者：De-Long Kong Ye Huang Lai-Yang Ren Wen-Hua Feng 

作者机构：Department of New Drug Research and DevelopmentInstitute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2015年第26卷第6期

页      面：790-792页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 10[医学] 

基　　金：financially supported by the National Science and Technology Major Project of China (No.521042) 

主　　题：Bedaquiline Inactive stereoisomers RecycleCsp3 Csp3 cleavage 

摘      要：Bedaquiline is a new medicine for pulmonary multi-drug resistant tuberculosis （MDR-TB）, which is a pure enantiomer with two chiral centers. The current industrial preparation process requires the separation of active Bedaquiline from a mixture of four isomers. Obviously, direct dispose of the other three undesired stereoisomers will cause significant waste and increase the unnecessary cost of production. Here, we developed an efficient, facile and scalable process for recycling the inactive stereoisomers of Bedaquiline. All these inactive stereoisomers could be recycled by their conversion to two important intermediates in the Bedaquiline synthesis via a base-catalyzed Csp3-Csp3 bond cleavage of a benzyl alcohol intermediate. And the precise conditions and mechanism of the base-catalyzed cleavage reaction were discussed.