Li Yunshan, Zhang Jingyang, Chen Yi, Pang Jiahua, Chen Yuejie, Tang Yefeng
School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, 100084, Beijing, China.
Angew Chem Int Ed Engl. 2025 Jan 10;64(2):e202414985. doi: 10.1002/anie.202414985. Epub 2024 Nov 7.
An unprecedented dyotropic rearrangement of β-lactams has been developed, which provides an enabling tool for the synthesis of structurally diverse γ-butyrolactams. Unlike the well-established dyotropic rearrangements of β-lactones, the present reaction probably proceeds through a dual-activation mode, and thus displays unusual reactivity and chemoselectivity. The combined computational and experimental results suggest that the dyotropic rearrangement of β-lactams may proceed through different mechanisms depending on the nature of migrating groups (H, alkyl, or aryl). Hinging on a chemoselective H-migration dyotropic rearrangement of β-lactams, we have completed the divergent synthesis of tricyclic marine alkaloids (-)-lepadiformine A, (+)-cylindricine C, and (-)-fasicularin within 11-12 longest linear steps.
已开发出一种前所未有的β-内酰胺的双烯异构重排反应，该反应为合成结构多样的γ-丁内酯提供了一种有效工具。与已成熟的β-内酯双烯异构重排不同，本反应可能通过双重活化模式进行，因此表现出不同寻常的反应活性和化学选择性。计算和实验结果相结合表明，β-内酰胺的双烯异构重排可能根据迁移基团（氢、烷基或芳基）的性质通过不同机制进行。基于β-内酰胺的化学选择性氢迁移双烯异构重排反应，我们在11-12步最长线性步骤内完成了三环海洋生物碱（-）-lepadiformine A、（+）-cylindricine C和（-）-fasicularin的发散合成。
