HPPO-Derived Meroterpenoids from the Marine-Derived Fungus Penicillium sp. SCSIO 41691.

Seven new 4-hydroxy-6-phenyl-2 H -pyran-2-one (HPPO) derived meroterpenoids, 1-methyl-12a,12b-epoxyarisugacin M ( 1 ), 1-methyl-4a,12b-epoxyarisugacin M ( 2 ), 2,3-dihydroxy-3,4a-epoxy-12a-dehydroxyisoterreulactone A ( 3 ), 2-hydroxy-12a-dehydroxyisoterreulactone A ( 4 ), 3'-demethoxyterritrems B' ( 5 ), 4a-hydroxyarisugacin P ( 6 ), and 1-epi-arisugacin H ( 7 ), together with two known analogues ( 8 and 9 ), were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41691. Their structures were elucidated by spectroscopic methods, and the absolute configurations of compounds 1 and 3 were determined by single-crystal X-ray diffraction. Among them, 1 and 2 had a unique methyl migration in the basic meroterpenoid skeleton with a 12a,12b-epoxy or 4a,12b-epoxy group, and 3 was a highly oxygenated HPPO-derived meroterpenoid featuring a rare 6/5/6/6/6/6 hexacyclic system with a 3,4a-epoxy group. Biologically, 5 exhibited inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC 50 value of 21 μM, more potent than the positive control indomethacin.