特拉万星的合成  

Synthesis of telavancin

作　　者：马帅[1] 贾景雨[1] 袁红[1] 曹胜华[1] 

机构地区：[1]中国医药集团总公司四川抗菌素工业研究所,成都610052

出　　处：《中国新药杂志》2013年第23期2809-2812,共4页Chinese Journal of New Drugs

摘　　要：目的:新型脂糖肽类抗生素特拉万星的合成及工艺优化。方法:以癸胺、乙二醛二甲基缩醛为原料经还原胺化反应,用氯甲酸-9-芴甲酯保护亚氨基、盐酸水解缩醛制得N-(9-芴基甲氧羰基)-癸基氨基乙醛(9)。盐酸万古霉素与9发生还原胺化反应、再脱9-芴甲氧羰基保护基、与氨甲基膦酸进行曼尼希反应合成目标产物特拉万星。结果:以盐酸万古霉素为原料计,该合成路线的总收率为40.97%。特拉万星的结构经MS和1H-NMR谱确证。结论:该合成路线操作简单、试剂价廉易得,反应条件进行了优化,提高了收率。Objective： To synthesize telavancin and improve the synthetic process. Methods： Decylamine and glyoxal 1,1-dimethylacetal as the starting materials were reacted by reductive amination. 9-Fluorenylmethyl chloroformate was used to protect imino group, and hydrochloric acid hydrolyzed the acetal to afford N-Fmoc-decyl- aminoethanal （9）. Vancomycin hydrochloride was reacted with compound 9 by reductive amination, and then the 9-fluorenylmethoxycarbonyl group was deprotected, followed by reaction with aminomethylphosphonic acid by Man- nich reaction to provide the target compound. Results： The total yield of the synthetic route from vancomycin hydrochloride was 40.97%. The structure of telavancin was confirmed by MS and H-NMR. Conclusion： This op- timized synthetic route is easy to operate, the cost is lower and the yield is higher.

关 键 词：特拉万星 脂糖肽类抗生素 合成 工艺优化 

分 类 号：R914.5[医药卫生—药物化学]