厄他培南钠的合成研究  

Study on the synthesis of ertapenem sodium

作　　者：史颖[1] 李坤[1] 赵学斌[1] 吕健[1] 孙晓旺[1] 

机构地区：[1]石药集团中奇制药技术(石家庄)有限公司,石家庄050051

出　　处：《中国抗生素杂志》2011年第7期519-522,共4页Chinese Journal of Antibiotics

基　　金："十一五"重大新药创制项目:石药集团创新药物研制产学研联盟建设(项目编号:2008ZX09401-004)

摘　　要：目的开发目标化合物及其侧链放大工艺。方法以L-PNZ-羟脯为原料采用"一锅煮"工艺,通过硫内酯中间体制备厄他培南侧链,再经缩合、脱保护成盐合成目标化合物。结果目标化合物及中间体经红外光谱、核磁共振氢谱和质谱确证化学结构,厄他培南放大工艺总收率40%(以MAP计),纯度99.2%。结论该合成工艺为中试规模,收率高,易于实现产业化。Objective The development of a scaleable process for the manufacture of ertapenem involved the synthesis of side chain is described. Methods Beginning with N-PNZ-4-hydroxy- L-proline, an one-pot process of side chain via thiolactone was demonstrated. A telescoped sequence of condensation, deprotection and the formation of sodium salt generates the title compound. Results The key intermediates and ertapenem were characterized by IR, ^1HNMR and MS. The process has been successfully implemented to prepare several kilogram batches of the target compound in 40% overall yield and 99.2% area purity. Conclusion A pilot-plant suitable process of ertapenem with high yield and amenable to industrialization was provided.

关 键 词：厄他培南钠 硫内酯 缩合 脱保护 

分 类 号：R978.1[医药卫生—药品]