强力霉素的绿色合成

Green synthesis of doxycycline

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.