Meroterpenoid Synthesis via Sequential Polyketide Aromatization and Cationic Polyene Cyclization: Total Syntheses of (+)-Hongoquercin A and B and Related Meroterpenoids

Abstract

(+)-Hongoquercin A and B were synthesized from commercially available trans,trans-farnesol in six and eleven steps, respectively, using dual biomimetic strategies with polyketide aromatization and subsequent polyene functionalization from a common farnesyl-resorcylate intermediate. Key steps involve Pd(0)-catalyzed decarboxylative allylic rearrangement of a dioxinone β,δ-diketo ester to a β, δ-diketo dioxinone, which was readily aromatized into the corresponding resorcylate, and subsequent polyene cyclization via enantioselective protonation or regioselective terminal alkene oxidation and cationic cyclization of enantiomerically enriched epoxide to furnish the tetracyclic natural product cores. Analogues of the hongoquercin were synthesized via halonium-induced polyene cyclizations, and the meroterpenoid could be further functionalized via saponification, hydrolytic decarboxylation, reduction, and amidation reactions.