Meroterpenoids with diverse ring systems from the sponge-associated fungus Alternaria sp. JJY-32

Fifteen meroterpenoids (1-15) with diverse ring systems including an unprecedented oxaspiro[5.5]nonane-fused cyclohexenone (1), hydrogenated benzofurans (2-5), hydrogenated chromans (6, 7), hydrogenated cyclopenta[b]chromans (8-11), and four monocyclic structures (12-15) were isolated from the sponge-associated fungus Alternaria sp. JJY-32. The structures were elucidated by detailed spectroscopic analysis, including 2D NMR and electronic circular dichroism (ECD) calculations, and assisted by chemical derivatizations. On the basis of supplementation experiments with specific enzyme inhibitors and putative precursors, a shikimate-isoprenoid hybrid biosynthetic pathway is proposed. The NF-κB inhibitory activities of 1-15 were tested, and all of them, except 6 and 7 (IC50 > 100 μM), showed activities with IC50 values ranging from 39 to 85 μM in RAW264.7 cells.