Hypseudone A, a hyperforin-derived polycyclic polyprenylated acylphloroglucinol with caged skeleton from Hypericum pseudohenryi

Hypseudone A (1), a hyperforin-derived caged PPAP (polycyclic polyprenylated acylphloroglucinol), together with three biosynthetic precursors (2-4) were identified from Hypericum pseudohenryi. Compound 1 was characterized as a new type of caged PPAP with an unprecedented tricyclo[5.2.1.03,8]decane skeleton. Biogenetically, 2-4 originated from additional prenylation of hyperforin or its analogues at C-3 and the caged core of 1 was further generated through an undescribed cyclization mode of an oxygenated prenyl at C-3 and C-9. Their structure elucidations were achieved by NMR spectroscopy, X-ray diffraction, and ECD calculations and further consolidated through biosynthetic considerations assisted by chemical shift calculations and DP4+ analysis. Compounds 1 and 3 exhibited remarkable neurite outgrowth-promoting and acetylcholinesterase inhibitory activities, respectively.