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

(+)-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.