Hyperforones A–C, benzoyl-migrated [5.3.1]-type polycyclic polyprenylated acylphloroglucinols from Hypericum forrestii

Abstract

Three unprecedented benzoyl-migrated polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforones A–C (1–3), were isolated from Hypericum forrestii, together with a new benzoyl-substituted analogue (4) of hyperforin. Compounds 1–3 are the first examples of naturally occurring benzoyl-PPAPs with a unique C-1 H-substituted bicyclo[5.3.1]hendecane scaffold. Their structures and absolute configurations were established by HRESIMS, NMR spectroscopy data, electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and gauge-independent atomic orbital (GIAO) NMR calculations with DP4+ analyses. A plausible biosynthetic formation of the benzoyl-migrated C-1 H-substituted bicyclo[5.3.1]hendecane skeleton in 1–3via a sterically favored hemiketalization/Retro-Claisen cascade was proposed. Bzhyperforin (4) showed significant cytotoxicity against MDA-MB-231 cells with an IC₅₀ value of 6.88 ± 1.37 μM.