拉考沙胺的合成工艺研究  

The Synthetic Research of Lacosamide

作　　者：张之建 刘可可 刘源 ZHANG Zhijian;LIU Keke;LIU Yuan(Shanghai Pharma Group(Changzhou)Kony Pharmaceutical Co.,Ltd.,Changzhou 213105,China)

机构地区：[1]上药康丽(常州)药业有限公司,江苏常州213105

出　　处：《生物化工》2022年第5期99-102,共4页Biological Chemical Engineering

摘　　要：拉考沙胺是近年来开发的用于治疗癫痫的药物,其合成工艺路线几经优化,目前大范围使用的第三代工艺存在手性副产物,纯化困难。以第三代拉考沙胺合成路线为基础,通过过程优化,引入L-酒石酸这一手性拆分剂,提高拉考沙胺关键中间体的手性纯度至99%以上,从而减少拉考沙胺的纯化步骤;以Boc-D-丝氨酸计,拉考沙胺的收率为63%,与现有报道的合成工艺比,提高了原子利用率。Lacosamide is a drug developed in recent years for the treatment of epilepsy, and its synthesis process route has been optimized several times, and the third-generation process currently widely used has chiral by-products and is difficult to purify. Based on the third-generation lacosamide synthesis route, through process optimization,L-tartaric acid, a chiral splitter, is introduced to improve the chiral purity of the key intermediate of lacosamide to more than 99%, thereby reducing the purification steps of lacosamide. In terms of Boc-D-serine, the yield of lacosamide is 63%, which improves the atomic utilization rate compared with the existing reported synthesis process.

关 键 词：拉考沙胺 L-酒石酸 手性纯度 

分 类 号：R914.5[医药卫生—药物化学]