Buccini Marco, Tham Louisa, Dhoro Francis, Skelton Brian W, Williams Craig M, Piggott Matthew J
Chemistry, School of Molecular Sciences, University of Western Australia, Perth 6009, Australia.
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane 4072, Queensland, Australia.
ACS Omega. 2022 Jun 1;7(23):19080-19092. doi: 10.1021/acsomega.2c02116. eCollection 2022 Jun 14.
Model chemistry involving the bisannulation of 2,3-dichloro-1,4-naphthoquinone with the ester enolate derived from ethyl -nitrophenylacetic acid, which rapid assembled the ABCD ring system of a pentacyclic pyrroloacridine, has been applied to the attempted synthesis of the marine natural product alpkinidine. The reaction of ethyl -nitrophenylacetic acid with 6,7-dichloro-2-methylisoquinoline-1,5,8(2)-trione, required to extend the model strategy to alpkinidine, was unfruitful, giving only complex mixtures. Efforts to direct the regiochemistry of the key Michael substitution step using 6-bromo-2-methylisoquinoline-1,5,8(2)-trione afforded an adduct sharing the complete carbon skeleton of alpkinidine, but this could not be elaborated to the natural product.
涉及2,3-二氯-1,4-萘醌与由乙基-硝基苯基乙酸衍生的酯烯醇盐进行双环化反应的模型化学，该反应快速构建了五环吡咯并吖啶的ABCD环系统，已应用于尝试合成海洋天然产物阿尔平尼定。将模型策略扩展至阿尔平尼定所需的乙基-硝基苯基乙酸与6,7-二氯-2-甲基异喹啉-1,5,8(2)-三酮的反应未成功，仅得到复杂混合物。使用6-溴-2-甲基异喹啉-1,5,8(2)-三酮来指导关键迈克尔取代步骤的区域化学的努力得到了一个与阿尔平尼定具有完整碳骨架的加合物，但无法将其转化为天然产物。
