摘要
目的优化万古霉素N^4氨基还原烷基化的反应条件。方法以万古霉素为原料,筛选还原烷基化反应的溶剂、还原剂、醛用量和反应温度,用HPLC方法测定原料和产物含量。结果确立了以甲醇/二甲基亚砜=1:1为溶剂、硼烷叔丁胺为还原剂、1.3倍醛用量、缩合温度65℃、还原温度为室温的最优反应条件。结论利用本文优化后的条件可以有效合成万古霉素N4氨基还原烷基化产物,研究结果为其他糖肽类抗生素的半合成衍生化提供技术基础。
Objective To optimize the N4-reductive alkylation conditions of vancomycin. Methods Vancomycin was used as the starting material. The solvents, the reducing agents, the ratios of aldehyde and the temperatures were optimized. The contents of vancomycin and the products were determined by HPLC canalysis. Results The preferred conditions were as the following： MeOH/DMSO=1：1 as solvent, tert-butylamine borane as the reducing agent, 1.3eq of aldehyde, 65 ℃ as the condensation temperature and room temperature as the reduction temperature. Conclusion The optimized method is efficient to synthesize the N4-reductive alkylation product of vancomycin. This result can also provide a technical basis for the semi-synthesis of other glycopeptide antibiotics.
作者
邵昌
阮林高
戈梅
Shao Chang;Ruan Lin-gao;Ge Mei(Shanghai Laiyi Center for Biopharmaceutical R＆D,Shanghai 20024)
出处
《中国抗生素杂志》
CAS
CSCD
2018年第7期847-852,共6页
Chinese Journal of Antibiotics
基金
上海市科学技术委员会科研计划项目(No.14431906700)
关键词
万古霉素
还原烷基化
合成
Vancomycin
Reductive alkylation
Synthesis
