苏沃雷生的合成研究进展  

Research Progress in The Synthesis of Suvorexant

作　　者：韩冰冰 侯建 邱迅 陈再新 HAN Bingbing;HOU Jian;QIU Xun;CHEN Zaixin(Jiangsu Bioscene Pharmaceutical Co.,Ltd.,Changzhou 213125,China)

机构地区：[1]江苏百奥信康医药科技有限公司,江苏常州213125

出　　处：《合成化学》2024年第7期673-684,共12页Chinese Journal of Synthetic Chemistry

摘　　要：苏沃雷生(Suvorexant)由默沙东公司首研上市,是首个被批准上市的食欲素受体拮抗剂,临床上用于治疗以睡眠开始和/或睡眠维持困难为特征的失眠。本文对苏沃雷生原料药的合成路线进行了分析、总结和概括,并将合成路线分成两个大类进行总结。第一类为片段拼接,在片段拼接合成方法中,关键的手性中间体有拆分的方法和手性起始原料法。手性起始原料法因不需要拆分,收率高,具有较好的产业化价值。第二类为顺序合成,其中钌催化具有较高收率,而酶催化避免了使用卤代溶剂和重金属,符合绿色化学理念,在未来发展中更具优势。本文总结的相关路线内容为苏沃雷生的产业化研究提供参考。Suvorexant,first developed and marketed by Merck&Co.,is the first approved orexin receptor antagonist for the clinical treatment of insomnia characterized by difficulty in sleep onset and/or sleep maintenance.In this paper,the synthetic routes of suvorexant will be analyzed,summarized and into two categories.The first type is fragment splicing.In the synthesis method of fragment splicing,the key chiral intermediates are prepared by resolution method and chiral starting material method.The chiral starting material method has good industrialization value due to high yield,since it does not require separating the material.The second kind of synthesis method is sequential synthesis,in which ruthenium catalysis has a higher yield,while enzyme catalysis avoids the use of halogenated solvents and heavy metals,which accords with the concept of green chemistry and has more advantages in future development.The relevant routes summarized in this paper provide a reference for its industrialization.

关 键 词：苏沃雷生 食欲素受体拮抗剂 合成 手性拆分 钌催化 酶催化 

分 类 号：TQ460.1[化学工程—制药化工]