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.