: This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer‐Villiger oxidation of cyclohexanone, which was developed to produce seven‐membered lactones and establish the required stereochemistry at the C14 position (92% yield, 99% ee, 500 mg scale). Cis‐ and trans‐tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid‐triggered, tunable acyl‐Pictet‐Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl‐Pictet‐Spengler cyclization cascade. By strategically using these two reactions and the late‐stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.

中文翻译：

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塔卡曼生物碱的立体发散全合成


：本文描述了塔卡曼生物碱的简洁、不对称和立体发散全合成。该合成的关键步骤是环己酮的生物催化拜尔-维利格氧化，其开发用于生产七元内酯并在 C14 位建立所需的立体化学（产率 92%，ee 99%，500 mg 规模）。顺式和反式四环吲哚喹啉西啶支架通过酸触发的、可调节的酰基-Pictet-Spengler型环化级联快速合成，作为构建生物碱骨架的关键反应。计算结果表明，氢键对于稳定中间体和在酰基-Pictet-Spengler 环化级联过程中诱导不同的加成反应至关重要。通过策略性地利用这两个反应以及功能化吲哚喹啉西啶核心的后期多样化，实现了八种塔卡曼生物碱的不对称全合成。这项研究可能会推进与塔卡曼生物碱药物化学相关的研究。