Lagarocladone A, a Polycyclic Polyprenylated Acylphloroglucinol Featuring an Unprecedented Skeleton from Hypericum lagarocladum.

Lagarocladone A (1), a novel polycyclic polyprenylated acylphloroglucinol (PPAP) with a highly rearranged skeleton, along with a new spiro-PPAP, lagarocladone B (2), and three known analogues (3-5), were isolated from the aerial parts of Hypericum lagarocladum. Compound 1 possesses an unprecedented 6/6/5/5/6/5 ring system featuring a spiro[2-oxa-bicyclo[4.3.0]nonane-4,6'-tetracyclo[10.4.0.03,10.04,8]hexadecane] core. Their structures were elucidated by comprehensive spectroscopic data analysis, CASE algorithms, quantum 13C NMR DP4+, and electronic circular dichroism calculations. Significantly, compound 1 exhibited hepatoprotective activity against APAP-induced cytotoxicity in HepG2 cells, potentially through attenuating oxidative stress and preserving membrane integrity.