Hyperforatone A, the 1,8-seco rearranged polycyclic polyprenylated acylphloroglucinol with a unique bicyclo[5.4.0]undecane core from Hypericum perforatum

Abstract

Hyperforatone A (1), the 1,8-seco rearranged polycyclic polyprenylated acylphloroglucinol, possessed an unusual bicyclo[5.4.0]undecane skeleton bearing a 5/7/6/5 ring system, and two known biosynthetically related precursors (2 and 3) were isolated from Hypericum perforatum (St. John's wort). The structure and absolute configuration were unambiguously confirmed by a combination of comprehensive spectroscopic data, computational methods including residual dipolar couplings (RDCs), and X-ray crystallography. Density functional theory (DFT) calculations revealed that the cationic cyclization reaction was key to proposed formation mechanism for hyperforatone A. Furthermore, in vitro and in vivo experiments demonstrated that compound 1 was a potential anti-neuroinflammatory agent.