Paralemnanoids A-K, new norsesquiterpenoids and sesquiterpenoids with hepatoprotective activity from the soft coral Paralemnalia sp.

UNLABELLED: Eleven nardosinane-type compounds, including a norsesquiterpenoid featuring a novel carbon skeleton designated as paralemnanoid A (1), and ten additional norsesquiterpenoids identified as paralemnanoids B - K (2 - 11), were isolated from the South China Sea soft coral Paralemnalia sp.. Comprehensive structural elucidation of compounds 1 - 11 was achieved through an integrated analytical approach, combining including NMR spectroscopy, HRESIMS, single-crystal X-ray diffraction analysis, DP4 + probability assessments, ECD calculations, and literature comparisons. Furthermore, we proposed that the novel poly-isoprenoid scaffold paralemnanoid A (1) originates from paralemnanoid B (2) through sequential oxidative modifications followed by non-enzymatic skeletal rearrangements. The hepatoprotective effects of compounds 1 - 11 were assessed through bioassays, revealing that paralemnanoids A (1) and E (5) exhibited moderate hepatoprotective activity at a concentration of 20 μmol/L in the zebrafish model. This study expands the chemical diversity of marine-derived nardosinane-type terpenoids and provides new insights into their potential therapeutic applications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s42995-025-00339-0.