A Novel Synthesis of the Racemic Lactone Ring of Camptothecin
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.
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