Biosynthetically Inspired Divergent Syntheses of Merocytochalasans
Biosynthetically Inspired Divergent Syntheses of Merocytochalasans
复制标题
细胞分裂素的生物合成启发发散合成
DOI：
10.1016/j.chempr.2020.11.010
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发表时间：
2021-01-14
期刊：
影响因子：
23.5
通讯作者：
Deng, Jun
中科院分区：
文献类型：
--
作者：
Long, Xianwen;Wu, Hai;Deng, Jun
合胞菌(Asperchalasine、epicochalasine、Aspergilasine、Asperflavipine和Amichalasines)是一类具有有趣结构和抗癌活性的真菌代谢产物。它们起源于独特的生物合成途径，导致表观蛋白和aspochalasin D基序的整合。需要一条简明、可扩展和发散的合成路线来制备足够数量的用于生物学研究的美胞胞松散衍生物。在这里，我们报道了一种生物启发的模块化合成方法，利用邻苯二酮中间体的仿生[5+2]杂环加成反应合成了一系列单胞松果糖。这一新的战略方法现在已经使几种天然产物的不同合成成为可能，包括表沙拉菌素A和B，曲霉素A-D，阿司匹林A和B，以及amichalasine A和B。我们以生物启发的方法制备这些硫胞松弛素，反过来可能有助于阐明硫胞松弛素同系物的生物合成途径，并使未来发现尚未分离的天然产物成为可能。
Merocytochalasans (asperchalasines, epicochalasines, aspergilasines, asperflavipines, and amichalasines) are a class of fungal metabolites with intriguing structures and anti-cancer activity. They stem from unique biosynthetic pathways that lead to the incorporation of epicoccine and aspochalasin D motifs. A concise, scalable, and divergent synthetic route is needed to enable the preparation of sufficient quantities of merocytochalasan derivatives for biological studies. Here, we report a bioinspired modular syntheses of a suite of merocytochalasans by taking advantage of a biomimetic [5+2] heterocycloaddition of an ortho-quinone intermediate. This novel strategic approach has now made possible the divergent syntheses of several natural products, including epicochalasines A and B, asepergilasines A-D, asperflavipines A and B, and amichalasines A and B. Our bioinspired approach to the preparation of these merocytochalasans may, in turn, help to elucidate the biosynthetic pathway of merocytochalasans congeners and enable the future discovery of natural products not yet isolated.