State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, CAS, University of Chinese Academy of Sciences, 345 Lingling Lu, Shanghai, 200032, China.
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
Angew Chem Int Ed Engl. 2022 Aug 22;61(34):e202207360. doi: 10.1002/anie.202207360. Epub 2022 Jul 13.
A facile method for the construction of the aspidosperma core from indoles functionalized with a nonterminal N-allenamide and dimethyl methylenemalonate is described. Various polysubstituted tetracyclic spiroindolines (27 examples) were afforded in good yields (61-90 %) with >99/1 dr and >99/1 Z/E selectivity under mild conditions. The annulation reaction provides straightforward access to the tetracyclic spiroindoline skeleton with substituents at the C5 position occurring in many natural products. As an application of this reaction, the total synthesis of three important natural products, (-)-deoxoapodine, (-)-kopsifoline D and (±)-melotenine A, was possible in short routes from tryptamine.
描述了一种从吲哚出发，通过非末端 N-烯丙酰胺和二甲亚甲基丙二酸二甲酯官能化构建阿皮斯多玛核心的简便方法。在温和条件下，各种多取代的四环螺[吲哚啉-3,4'-吡咯]（27 个实例）以良好的收率（61-90%）、>99/1 dr 和 >99/1 Z/E 选择性得到。该环化反应为具有许多天然产物中 C5 位取代基的四环螺[吲哚啉]骨架的构建提供了直接途径。作为该反应的应用，从色胺出发，通过短路线实现了三个重要天然产物（-）-去氧阿朴啡碱、（-）-kopisifoline D 和（±）-melotenine A 的全合成。
