Meroterpenoids Possessing Diverse Rearranged Skeletons with Anti‐inflammatory Activity from the Mangrove‐Derived Fungus Penicillium sp. HLLG‐122

Comprehensive Summary Fifteen new meroterpenoids, littoreanoids A—O ( 1 — 15 ), including three rearranged skeleton meroterpenoids ( 1 — 3 ), were isolated from the mangrove‐derived fungus Penicillium sp. HLLG‐122. Compound 1 was a novel berkeleyacetal‐derived meroterpenoid featuring an unusual spirocyclic 2‐oxaspiro[5.5]undeca‐4,7‐dien‐3‐one moiety. Compound 2 possessed an unusual 6/6/6/6/6 pentacyclic system with a novel 1‐hydroxy‐7,7‐dimethyl‐2‐oxabicyclo[2.2.2]octan‐5‐yl acetate moiety. Compound 3 was an unusual 6/7/6/5/6/5/4 polycyclic systems containing a β ‐lactone ring. The structures and absolute configurations of new compounds were elucidated by HRESIMS, NMR spectroscopy, single crystal X‐ray diffraction analysis, and electronic circular dichroism calculations. The plausible biosynthetic pathways of 1 — 3 were also proposed. Compounds 6 and 11 exhibited anti‐inflammatory effects with IC 50 values of 30.41 and 19.02 μmol/L, respectively. The bioactive compound 11 was selected for the investigation of preliminary mechanism using molecular docking and Western blotting experiments. Compound 11 could suppress the levels of TNF‐ α and IL‐6, and down‐regulate the protein expression of iNOS and COX‐2 in RAW 264.7 cells.