The Furan Shuffling Hypothesis: A Biogenetic Proposal for Eremophilane Sesquiterpenoids

Based on the structural similarities of the recently isolated eremophilane‐type sesquiterpenoids microsphaeropsisin B and C and the iso‐eremophilane periconianone C, a revised biogenetic hypothesis for C8–C11‐connected iso‐eremophilanes is presented and corroborated by strong experimental evidence. The first enantioselective total syntheses of microsphaeropsisin B and C were achieved starting from a known intermediate, whose synthesis was elaborated previously in the total synthesis of periconianone A, and in a total of 15 steps starting from γ‐hydroxy carvone. Mild reaction conditions for the subsequent α‐ketol rearrangement not only resulted in the herein proposed conversion of microsphaeropsisin B into periconianone C, but also in the conversion of microsphaeropsisin C into 4‐epi‐periconianone C. Shuffle the rings: An unusual furan rearrangement biogenetically connecting the eremophilane natural product microsphaeropsisin B and its regioisomer periconianone C is postulated. Strong experimental support for this intriguing mechanistic pattern is provided by total synthesis, with an α‐ketol rearrangement.