Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
Department of Chemistry, University of California─Davis, Davis, California 95616, United States.
J Am Chem Soc. 2024 Aug 7;146(31):21250-21256. doi: 10.1021/jacs.4c07900. Epub 2024 Jul 25.
Herein, we report concise total syntheses of diterpene natural products (-)-crinipellins A and B with a tetraquinane skeleton, three adjacent all-carbon quaternary centers, and multiple oxygenated and labile functional groups. Our synthesis features a convergent Kozikowski β-alkylation to unite two readily available building blocks with all the required carbon atoms, an intramolecular photochemical [2 + 2] cycloaddition to install three challenging and adjacent all-carbon quaternary centers and a 5-6-4-5 tetracyclic skeleton, and a controlled Cargill rearrangement to rearrange the 5-6-4-5 tetracyclic skeleton to the desired tetraquinane skeleton. These strategically enabling transformations allowed us to complete total syntheses of (-)-crinipellins A and B in 12 and 13 steps, respectively. The results of quantum chemical computations revealed that the Bronsted acid-catalyzed Cargill rearrangements likely involve stepwise paths to products and the AlR-catalyzed Cargill rearrangements likely involve a concerted path with asynchronous alkyl shifting events to form the desired product.
在此，我们报告了具有四环烷骨架、三个相邻全碳季碳中心和多个含氧及不稳定官能团的二萜天然产物（-）-刺鱼藤素 A 和 B 的简洁全合成。我们的合成采用会聚型 Kozikowski β-烷基化反应，将两个易得的砌块与所有所需的碳原子结合在一起，采用分子内光化学 [2 + 2] 环加成反应来安装三个具有挑战性和相邻的全碳季碳中心和一个 5-6-4-5 四环骨架，采用受控的 Cargill 重排反应将 5-6-4-5 四环骨架重排成所需的四环烷骨架。这些策略性的转化使我们能够分别以 12 步和 13 步完成（-）-刺鱼藤素 A 和 B 的全合成。量子化学计算的结果表明，布朗斯台德酸催化的 Cargill 重排可能涉及分步途径到产物，而 AlR 催化的 Cargill 重排可能涉及协同途径，其中存在异步烷基迁移事件以形成所需产物。
