Hyperpatone A (1), a highly oxidated polycyclic polyprenylated acylphloroglucinol (PPAP), along with a biosynthesized related PPAP (2) was isolated from Hypericum patulum under the guidance of LC-MS investigation. Architecturally, compound 1 represents the first PPAP with an unprecedented 8/6/5/6/5 pentacyclic skeleton and an intramolecular peroxy bridge, which might be derived from the [3.3.1]-type bicyclic polyprenylated acylphloroglucinol via the critical Baeyer-Villiger oxidation, decarboxylation, and intramolecular cyclization. The structures were established by extensive spectroscopic analysis, ACD software calculation, and quantum chemical computations. A plausible biogenetic pathway of 1 and 2 was also proposed. Importantly, both compounds exhibited moderate cytotoxic activities against the HEL cell line with the IC50 values ranging from 10.2 to 19.2 μM. Moreover, compound 1 showed an inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells at a lower concentration of 5 or 1 μM.