METHOD OF SYNTHESIS FOR CAMPTOTECIN-BOUND COMPOUNDS

摘要

FIELD: organic synthesis. ^ SUBSTANCE: invention relates to synthesis of camptotecin analogues from 2'-amino-5'-hydroxypropiophnone corresponding to AB ring portion of camptotecin structure and tricyclic ketone converted into CDE ring portion in camptotecin structure. Preparation of 2'-amino-5'-hydroxypropiophnone comprises following steps: (1) preparing compound (b) by mixing compound (a), benzylation agent, and a base followed by stirring mixture obtained in solvent on heating under reflux; (2) preparing compound (c) by dropwise adding Grignard reagent to compound (b) under an inert gas atmosphere; (3) preparing compound (d) by mixing compound (c) with an oxidant and stirring resulting mixture; and (4) preparing compound (e) via catalytic reduction of compound (d) (see scheme 1 below). Intermediate compounds (c') and (d') are described. Also described is a method for preparing tricyclic ketone to provide efficient complete synthesis of camptotecin serving as starting compound for irinotecan hydrochloride and a various types of camptotecin derivatives as well as for stable preparation of camptotecin and its derivatives. Scheme 1: . ^ EFFECT: expanded synthetic possibilities in camptotecin derivatives series. ^ 5 cl, 17 tbl, 33 ex