拓扑替康中三个有关物质的合成

Syntheses of Three Compounds Related to Topotecan

采用易得的原料、简单的化学方法和方便的操作,设计了新的合成路线,制备了拓扑替康药物报批中的三种相关杂质。分别由拓扑替康盐酸盐(1)经游离、酯水解开环反应制备得到了拓扑替康羧酸钠盐(2),由拓扑替康(11)经正丙醇取代反应制备得到9-丙氧甲基-10-羟基喜树碱(4),以及由10-羟基喜树碱(5)经羟甲基化反应制备得到9-羟甲基-10-羟基喜树碱(3)。

Three related impurities, i.e. topotecan carboxylic acid sodium salt （2）, 9-propoxymethyl-10- hydroxycamptotheein （4） and 9-hydroxymethyl-10-hydroxycamptothecin （ 3 ） , in the topotecan drug approval are synthesized based on new and practical routes, easily available materials, simple chemistry and convenient operations. Compound 2 is obtained by dissociating and esterolysis of topotecan hydrochloride （1） , 4 is synthesized by substitution reaction of n-propyl alcohol to topoteean （11） , and 3 is prepared by hydroxyl methylation reaction of 10-hydroxy camptothecin （ 5 ）.