Unified Total Synthesis of Phrymarolin and Haedoxan Natural Products.

ABSTRACT: We disclose a unified synthetic route to the furofuran lignans phrymarolin I and II as well as the insecticidal natural products haedoxan A and D. The furofuran core was constructed using a formal [3 + 2] cycloaddition between an α-silyloxy aldehyde and a styrene, followed by a samarium(II) iodide promoted-cyclization of a β-formyloxy ketone. While this sequence enabled the synthesis of phrymarolin I and II in eight steps, attempts to unmask the ortho-quinone necessary for a bioinspired formal [4 + 2] cycloaddition were unsuccessful, initially preventing access to the haedoxans. Revising the choice of the arene substitution pattern enabled the formation of the requisite ortho-quinone followed by a bioinspired cyclization to the 1,4-benzodioxane motif of the haedoxan framework

SUBMITTER: Paciorek J 

PROVIDER: S-EPMC7618468 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature