Liu Xin, Zhou Yun, Meng Yu, Zhu Qi, Li Renhe, Dong Guangbin
Department of Chemistry, University of Chicago, Chicago, Illinois, 60637, USA.
Angew Chem Int Ed Engl. 2025 Jun 2;64(23):e202502736. doi: 10.1002/anie.202502736. Epub 2025 Apr 10.
Concise total syntheses of five leuconoxine-type alkaloids, i.e., chloromelodinine, leuconodine A, leuconodine F, melodinine E, and leuconoxine, are achieved through a pyrrole-centered strategy. The approach features a newly developed palladium/norbornene-catalyzed pyrrole double C─H functionalization reaction to generate the core skeleton and a divergent oxidative dearomatization to complete the end game. In addition, no protecting group was employed, and the strategic use of a chloro substituent offers a number of advantages in these syntheses, which could have implications beyond this work. The discovery of an unusual chloro 1,2-migration reaction enabled the first total synthesis of chloromelodinine E. This work represents the shortest syntheses of these natural products to date with 10-11 total steps.
通过以吡咯为核心的策略，实现了五种亮甲藻毒素型生物碱（即氯美洛地宁、亮甲藻毒素A、亮甲藻毒素F、美洛地宁E和亮甲藻毒素）的简洁全合成。该方法的特点是新开发的钯/降冰片烯催化的吡咯双C─H官能团化反应以生成核心骨架，以及多样化的氧化脱芳构化反应以完成最终步骤。此外，未使用保护基团，并且氯取代基的策略性使用在这些合成中具有许多优势，这可能对本工作之外的领域产生影响。发现了一种不寻常的氯1,2-迁移反应，实现了氯美洛地宁E的首次全合成。这项工作代表了迄今为止这些天然产物最短的全合成，总共10-11步。
