外消旋喜树碱内酯环的合成新方法
A Novel Synthesis of the Racemic Lactone Ring of Camptothecin
任倩龙 1张丰旗 1朱书雷 2吕伟1
作者信息
- 1. 华东师范大学化学与分子工程学院,上海分子治疗与新药创制工程技术研究中心,上海 200062
- 2. 华东师范大学化学与分子工程学院,上海分子治疗与新药创制工程技术研究中心,上海 200062;华东师范大学药学院,人工智能与新药创智中心,上海 200062
- 折叠
摘要
该文报道了以6-氯-2-甲氧基烟酸(12)为起始原料,制备喜树碱中间体外消旋内酯环17的合成新路线.首先,12与筛选的1-(叔丁基二甲基硅氧基)丁-2-酮、进行亲核加成反应;然后,选用丙酮叉和苄基进行选择性保护;最后,经氧化、甲基磺酸脱保护、关环得目标产物.该工艺总收率31.23％(以12计).化合物17再经4步反应可制备喜树碱外消旋三元酮.该合成新方法成功地规避了使用诸如臭氧、四氧化锇和氰化物等危险化学试剂的需求,提高了安全性.
Abstract
A novel synthetic route for the preparation of the camptothecin intermediate,the racemic lactone(17),starting from 6-chloro-2-methoxynicotinic acid(12)was reported in this paper.Initially,compound 12 underwent a nucleophilic addition reaction with the selected l-(tert-butyldimethylsilyloxy)butan-2-one.Employing an acetal and a benzyl group for selective protection,the synthesis proceeded through oxidation,deprotection and cyclization with methylsulfonic acid.The overall yield of this process was 31.23％(based on 12).Compound 17 could be effectively converted into the racemic tricyclic ketone through four additional steps.This new synthetic method successfully avoided the needs for hazardous reagents such as ozone,osmium tetroxide,and cyanides,greatly enhanced the safety.
关键词
喜树碱/外消旋内酯环/全合成Key words
camptothecin/racemic lactone ring/total synthesis引用本文复制引用
出版年
2024
NETL
NSTL
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