Synthesis of Biologically Active Indenoisoquinoline Derivatives via a One-Pot Copper(II)-Catalyzed Tandem Reaction

A concise route for the synthesis of indenoisoquinoline derivatives from 2-iodobenzamide and 1,3-indanedione derivatives in the presence of copper­(II) chloride and cesium carbonate in acetonitrile solvent is reported. A wide variety of 2-iodobenzamide derivatives and indandiones could be used to synthesize indenoisoquinoline derivatives and other fused indenoisoquinoline in moderate to good yields. This methodology was adapted for the one-step synthesis of a series of clinically active topoisomerase I inhibitors such as NSC 314622, LMP-400, LMP-776.本研究报道了一条以2-碘苯甲酰胺（2-iodobenzamide）与1,3-茚二酮（1,3-indanedione）衍生物为原料，在氯化铜(II)（copper(II) chloride）和碳酸铯（cesium carbonate）存在下、以乙腈（acetonitrile）为溶剂合成茚并异喹啉（indenoisoquinoline）衍生物的简洁合成路线。该方法可兼容多种2-碘苯甲酰胺衍生物与茚二酮衍生物，能够以中等至优异的收率制备茚并异喹啉衍生物及其他稠合茚并异喹啉类化合物。此合成策略可用于一步制备一系列临床活性的拓扑异构酶I（topoisomerase I）抑制剂，如NSC 314622、LMP-400及LMP-776。