(S)-N-叔丁氧羰基-3-羟基-1-金刚烷甘氨酸的合成  

Synthesis of (S)-N-Boc-3-hydroxyadamantylglycine

作　　者：王建塔[1] 陈瑞[1] 张毅[1] 徐黔江[1] 汤磊[1] 

机构地区：[1]贵州医科大学,贵州贵阳550004

出　　处：《广州化工》2017年第11期45-47,共3页GuangZhou Chemical Industry

基　　金：贵州省卫生计生委科学技术基金(gzwjkj2014-2-102);贵州省科技厅中药现代化项目(黔科合ZY字[2013]3019号);贵州省科技厅社发攻关项目(黔科合SY字[2015]3030);贵州省普通高等学校药物化学工程研究中心建设项目(黔教合KY字[2014]219)

摘　　要：研究通过化学合成法制备沙格列汀关键中间体(S)-N-叔丁氧羰基-3-羟基-1-金刚烷甘氨酸。以溴代金刚烷为起始原料,经亲核取代、混酸氧化、碱水解、肟化反应、催化氢化、氨基保护以及手性拆分等7步反应获得目标产物。所制备目标产物的总收率17.1%,光学纯度98.7%。本合成工艺稳定,操作简便,条件温和,适合(S)-N-叔丁氧羰基-3-羟基-1-金刚烷甘氨酸工业化生产。The process for synthesis of （S）- N-Boc- 3- hydroxyadamantylglycine, a key intermediate for the preparation of saxagliptin, was studied. It was synthesized by 1 -bromoadamantane via nucleophilic substitutions, oxidation, hydrolization, oximation, catalytic hydrogenation, amino protection to give desired （S）- N- Boc- 3- hydroxyadamantylglycine. The product was synthesized at 17. 1%, with optical purity of 98.7%. The synthesis technology of （S）-N-Boc-3-hydroxyadamantylglycine had more advantages such as stable process, mild reaction condition and simple operation, was suitable for industrial production.

关 键 词：沙格列汀 中间体 (S)-N-叔丁氧羰基-3-羟基-1-金刚烷甘氨酸 拆分 

分 类 号：R914[医药卫生—药物化学]