Biosynthetically Inspired Divergent Syntheses of Merocytochalasans

•A bioinspired 5-step synthetic pathway to ten complex merocytochalasans•A [5+2] cycloaddition was applied forge the bicyclo[3.2.1]octadienone scaffold•Sunlight-promoted [2+2] and acyloin rearrangement•PMe3 initiated MBH-type reaction Although target-oriented synthesis can be effectively used achieve syntheses of specific natural products, divergent a series structurally biogenetically related products in modular, highly convergent, scalable manner remains challenge for community. Here, we describe biosynthetically inspired merocytochalasans enabled by rational analysis biosynthetic network different subtypes merocytochalasans, as well incorporation product precursors through Diels-Alder ring formation rearrangement reactions. This strategy not only enables sufficient quantities material further biological investigations but may also help decipher congeners enable discovery new future. Merocytochalasans (asperchalasines, epicochalasines, aspergilasines, asperflavipines, amichalasines) are class fungal metabolites with intriguing structures anti-cancer activity. They stem from unique pathways that lead epicoccine aspochalasin D motifs. A concise, scalable, route is needed preparation merocytochalasan derivatives studies. report modular suite taking advantage biomimetic heterocycloaddition an ortho-quinone intermediate. novel strategic approach has now made possible several including epicochalasines B, asepergilasines A-D, asperflavipines amichalasines B. Our these may, turn, elucidate future yet isolated. The design typically begins retrosynthetic target molecule order trace it back simpler easily available precursors.1Corey E.J. Cheng X.-M. Logic Chemical Synthesis. Wiley, 1995Google Scholar, 2Nicolaou K.C. Vourloumis D. Winssinger N. Baran P.S. art science total at dawn twenty-first century.Angew. Chem. Int. Ed. 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