强力霉素的绿色合成  

Green synthesis of doxycycline

作　　者：徐桂清 高原 吴斗灿 毛龙飞 董文佩 张银贵 姜玉钦 李伟 XU Gui-qing;GUO Yuan;WU Dou-can;MAO Long-fei;DONG Wen-pei;ZHANG Yin-gui;JINAG Yu-qin;LI Wei(School of Chemistry and Chemical Engineering,Henan Normal University,Henan Engineering Research Center of Chiral Hydroxyl Pharmaceutical,Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions,Ministry of Education,Xinxiang 453007,China;Hennan Ziweixing Chemistry Co.Ltd.,Xinxiang 4453011,China)

机构地区：[1]河南师范大学化学化工学院,河南省手性醇类药物工程技术研究中心,精细化学品绿色制造河南省协同创新中心,绿色化学介质与反应教育部重点实验室,河南新乡453007 [2]河南紫微星化学有限公司,河南新乡4453011

出　　处：《化学研究与应用》2018年第10期1708-1712,共5页Chemical Research and Application

基　　金：河南省科技创新杰出青年基金项目(164100510015)资助;河南省重点科技攻关计划项目(152102310312)资助

摘　　要：强力霉素是一种在医药、林业、畜牧业等领域广泛使用的抗生素。本文以11α-氯代甲烯土霉素为起始原料,经脱氯、不对称氢化、成盐三步反应得到目标化合物。采用自己制备的催化剂,进行脱氯和不对称氢化两步反应,得到较好的化学和立体选择性,提高α-异构体的收率。并在此基础上提出α-6-脱氧土霉素对甲苯磺酸盐直接成盐制备强力霉素的方法,使产品收率大大提高,同时大大减少环境污染。三步总重量收率超过52%。该工艺适合工业化。Doxycycline hydrochloride is an important antibiotic used in pharmaceutical industry,forestry,animal husbandry and fishery industry.Starting from 11α-chloro-metacycline,doxycycline hydrochloride was synthesized through three steps and the overall yield was up to 52%.Chemoselectivity and stereoselectivity of the dechlorination and asymmetric hydrogenation steps were optimized using self-made catalyst.Furthermore,a direct salification method was found to increase the yield and greatly reduce environmental pollution on the base of the use of above catalyst.This procedure was suitable for industrialization.

关 键 词：强力霉素 成盐 绿色合成 

分 类 号：O643.3[理学—物理化学]