Buccini Marco, Dhoro Francis, Tham Louisa, 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, Queensland 4072, Australia.
ACS Omega. 2022 Jun 1;7(23):19093-19105. doi: 10.1021/acsomega.2c02117. eCollection 2022 Jun 14.
Strategies toward the total synthesis of the marine pyrroloacridine alkaloid alpkinidine have been explored, focusing on linking quinonoid CE ring-system synthons with the A ring, followed by condensation to form the B and D rings. The key Michael addition of the ester enolate derived from ethyl -nitrophenylacetate to 2-methylisoquinoline-1,5,8(2)-trione proceeded with the wrong regiochemistry. This issue was addressed by incorporating the D-ring nitrogen at an earlier stage, affording advanced intermediates possessing the complete carbon skeleton of alpkinidine. However, attempts to close the D and B rings were unsuccessful. The novel isoquinolinetriones reported here, and the general strategy of connecting CE- and A-ring synthons through Michael additions, may be useful in the synthesis of other pyrrolo- and pyridoacridines, in particular the anticancer lead neoamphimedine and analogues.
人们探索了海洋吡咯并吖啶生物碱阿尔平尼定的全合成策略，重点是将醌型CE环系合成子与A环连接，然后缩合形成B环和D环。由乙基 -硝基苯乙酸酯衍生的酯烯醇盐与2-甲基异喹啉-1,5,8(2)-三酮进行的关键迈克尔加成反应，其区域化学是错误的。通过在较早阶段引入D环氮解决了这个问题，得到了具有阿尔平尼定完整碳骨架的高级中间体。然而，闭合D环和B环的尝试未成功。本文报道的新型异喹啉三酮，以及通过迈克尔加成连接CE环和A环合成子的一般策略，可能有助于其他吡咯并吖啶和吡啶并吖啶的合成，特别是抗癌先导化合物新两性霉素及其类似物。
