文献类型：期刊文献

中文题名：特拉万星合成工艺研究

英文题名：Synthetic process of telavancin

作者：熊伦[1,2];管栋梁[2,3];李剑[1];黄蔚[2,3]

机构：[1]华东理工大学药学院,上海200237;[2]中国科学院上海药物研究所药物化学研究室,上海201203;[3]中国科学院大学,北京100049

年份：2017

卷号：48

期号：2

起止页码：172

中文期刊名：中国药科大学学报

外文期刊名：Journal of China Pharmaceutical University

收录：CSTPCD;;Scopus;WOS:【ESCI(收录号:WOS:000404096700007)】；北大核心:【北大核心2014】；CSCD:【CSCD2017_2018】；

基金：This study was supported by the National Natural Science Foundation of China (No. 21372238, No. 21572244)

语种：中文

中文关键词：万古霉素;特拉万星;合成工艺

外文关键词：vancomycin; telavancin; synthetic process

摘要：对特拉万星工艺路线进行了研究,以癸醇为原料,经甲磺酰化、乙醇胺亲核取代、Fmoc保护和Parikh-Doering氧化得到N-(9-芴基-9-甲氧羰基)癸基氨基乙醛(5)。盐酸万古霉素与5通过还原胺化反应、脱Fmoc保护、曼尼希反应制备得到特拉万星。本研究对还原胺化和曼尼希反应这两步关键反应进行了详细的研究,优化了反应条件。以万古霉素为起始原料,该路线总收率为46%。
New process reported the synthesis of telavancin using decyl alcohol as the starting material. After methanesulfonylation, nucleophilic substitution with ethanolamine, Fmoc protection, and Parikh-Doering oxidation, the intermdiate N-（9-fluorenyl-9-methoxycarbonyl）decylaminoethyl acetaldehyde（5）was obtained. Vancomycin hydrochloride and intermediate 5 were then subject to reductive amination reaction, Fmoc deprotection, and Mannich reaction to give the telavancin product. The process have been deeply studied on the two key reactions of reductive amination and Mannich reaction, and the reaction conditions have been optimized. The overall yield is 46% based on starting material vancomycin.