特拉万星合成工艺研究
Synthetic process of telavancin
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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%。Abstract: 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.
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Keywords:
- vancomycin /
- telavancin /
- synthetic process
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