四川大学陈芬儿团队报道了塔卡曼生物碱的立体发散全合成。相关研究成果发表在2024年7月1日出版的《德国应用化学》。

本文介绍了一种简明、不对称、立体发散的塔卡曼生物碱的全合成方法。该合成中的一个关键步骤是环己酮的生物催化Baeyer-Villiger氧化，其被开发用于生产七元内酯并在C14位置建立所需的立体化学（92%产率，99%ee，500 mg规模）。顺式和反式四环吲哚醌利嗪支架是通过酸触发的可调酰基Pictet-Spengler型环化级联反应快速合成的，这是构建生物碱骨架的关键反应。

计算结果表明，在酰基Pictet-Spengler环化级联反应中，氢键在稳定中间体和诱导不同的加成反应方面至关重要。通过战略性地利用这两个反应和功能化吲哚醌利嗪核的后期多样化，实现了八种塔卡曼生物碱的不对称全合成。

该项研究可能有助于推进他卡曼生物碱的药物化学研究。

附：英文原文

Title: Stereodivergent Total Synthesis of Tacaman Alkaloids

Author: Xiangtao Chen, Huijing Wang, Jie Zeng, Qiuhong Li, Tonghui Zhang, Qiaoyun Yang, Pei Tang, Fener Chen

Issue&Volume: 2024-07-01

Abstract: Abstract: 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.

DOI: 10.1002/anie.202407149

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202407149