A synthetic investigation into the biosynthesis of hypsampsone A

A simplified proposal for the biogenetic origin of hypsampsone A, a complex meroterpenoid, is supported by a bioinspired cascade reaction that rapidly assembles its polycyclic core. The key steps in both the proposed biosynthesis and the bioinspired cascade are a spontaneous intramolecular carbonyl-ene reaction, an α-hydroxy-β-diketone rearrangement and a terminating intramolecular aldol reaction. The feasibility of this model cascade reaction strongly suggests that hypsampsone A is a highly rearranged member of the polycyclic polyprenylated acylphloroglucinol (PPAP) family of natural products.