四环高原阿朴啡碱(+)-Crociflorinone及(+)-6a-epi-Crociflorinone的不对称全合成  

Total Synthesis of Tetracyclic Homoproaporphine Alkaloids (+)-Crociflorinone and (+)-6a-epi-Crociflorinone

作　　者：杨帆[1] 濮留洋 谢建华[1] 周其林[1] Fan Yang;Liuyang Pu;Jianhua Xie;Qilin Zhou(Frontiers Science Center for New Organic Matter,State Key Laboratory and Institute of Elemento-Organic Chemistry,College of Chemistry,Nankai University,Tianjin 300071;School of Chemistry and Chemical Engineering,University of South China,Hengyang,Hunan 421001)

机构地区：[1]南开大学化学学院、元素有机化学国家重点实验室、有机新物质创造前沿科学中心,天津300071 [2]南华大学化学化工学院,湖南衡阳421001

出　　处：《有机化学》2025年第3期969-976,共8页Chinese Journal of Organic Chemistry

基　　金：基金资助:国家自然科学基金(92256303);国家自然科学基金(22221002);国家自然科学基金(22188101)。

摘　　要：四环高原阿朴啡碱是一类具有四氢异喹啉稠合螺环骨架结构的异喹啉生物碱. 在前期完成五环高原阿朴啡碱不对称全合成的基础上, 本研究以含有季碳中心的三环手性环己酮(–)-5为起始原料, 发展了Wittig反应和Pictet-Spengler环化为关键步骤的构筑含有螺环和季碳手性中心的五环手性骨架结构的策略, 并经逆oxa-Michael开环/甲基化串联等后期官能化修饰步骤, 实现了四环高原阿朴啡碱(+)-crociflorinone及其C6a位差向异构体(+)-6a-epi-crociflorinone的首次不对称全合成, 并确定其绝对构型.Tetracyclic homoproaporphine alkaloids are a subset of isoquinoline alkaloids bearing a tetrahydroisoquinoline- fused spiro skeleton. Building on the successful enantioselective total synthesis of pentacyclic homoproaporphine alkaloids, this study utilizes chiral tricyclic cyclohexanone (-)-5 containing a quaternary carbon center as the starting material and develops a strategy involving Wittig reaction and Pictet-Spengler cyclization as the key steps to construct the chiral penta- cyclic skeleton containing a spiro structure and a quaternary carbon center. Subsequently, through late-stage functionalization including a tandem retro-oxa-Michael reaction/methylation, the first asymmetric total synthesis of tetracyclic homoproapor- phine alkaloid (+)-crociflorinone alongside its C6a epimer (+)-6a-epi-crociflorinone was achieved, thereby confirming their absolute configurations.

关 键 词：四环高原阿朴啡碱 不对称全合成 crociflorinone Pictet-Spengler环化 异喹啉生物碱 

分 类 号：O626[理学—有机化学]