Hyperwightianols A-H, monoterpenoid demethylated acylphloroglucinol derivatives from Hypericum wightianum

Twelve undescribed optically pure monoterpenoid demethylated acylphloroglucinol derivatives, named hyperwightianols A-H (1-8), were isolated from the dried whole herb of Hypericum wightianum, along with ten structurally related known compounds (9-18). The structures of the new compounds were elucidated using UV spectroscopy, HRMS, and extensive 1D & 2D NMR experiments. Absolute configurations of the new compounds were determined via chiral HPLC resolution and electronic circular dichroism (ECD) calculations. Brewster's rule, experimental and computed NMR chemical shift analyses, and conformational studies were collectively employed to validate the configuration of the C-1 2-methylbutanoyl moiety. Compounds 4 and (±)-14 exhibited potent inhibitory activity against NO release in LPS-induced RAW264.7 cells, with IC₅₀ values of 9.56 ± 0.47 and 8.55 ± 1.10 μM, respectively.