Polycyclic Polyprenylated Acylphloroglucinol Congeners Possessing Diverse Structures from Hypericum henryi

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of hybrid natural products sharing the mevalonate/methylerythritol phosphate and polyketide biosynthetic pathways and showing considerable structural and bioactive diversity. In a systematic phytochemical investigation of Hypericum henryi, 40 PPAP-type derivatives, including the new compounds hyphenrones G–Q, were obtained. These compounds represent 12 different structural types, including four unusual skeletons exemplified by 5, 8, 10, and 17. The 12 different core structures found are explicable in terms of their biosynthetic origin. The structure of a known PPAP, perforatumone, was revised to hyphenrone A (5) by NMR spectroscopic and biomimetic synthesis methods. Several compounds exhibited inhibitory activities against acetylcholinesterase and human tumor cell lines. This study deals with the structural diversity, function, and biogenesis of natural PPAPs.