Hyparillums A and B: polycyclic polyprenylated acylphloroglucinols from Hypericum patulum

Hyparillums A (1) and B (2), two previously unidentified polycyclic polyprenylated acylphloroglucinols (PPAPs) with intricate architectures, were isolated from Hypericum patulum Thunb. Hyparillum A was the first PPAP with eight-carbon rings based on an unprecedented 6/6/5/6/6/5/6/4 octocyclic system featuring a rare heptacyclo[10.8.1.1^1,10.0^3,8.0^8,21.0^12,19.0^14,17]docosane core. In contrast, hyparillum B featured a novel heptacyclic architecture (6/6/5/6/6/5/5) based on a hexacyclo[9.6.1.1^1,9.0^3,7.0^7,18.0^11,16]nonadecane motif. Furthermore, hyparillums A and B demonstrated promising inhibitory effects on the proliferation of murine splenocytes stimulated by anti-CD3/anti-CD28 monoclonal antibodies and lipopolysaccharide, exhibiting half-maximal inhibitory concentration (IC₅₀) values ranging from 6.13 ± 0.86 to 12.69 ± 1.31 μmol·L^-1.