Biosynthetically Inspired Divergent Syntheses of Merocytochalasans

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.

Automated summary

Merocytochalasans are a class of fungal metabolites with intriguing structures and anti-cancer activity. A bioinspired modular synthesis approach has been developed to enable the preparation of various merocytochalasan derivatives, aiding in elucidating their biosynthetic pathways and potentially discovering new natural products.