Spiroeutypetides A and B, Polyketides with 5/6/5 and 6/6/5 Tricyclic Ring Systems Produced by the Marine-Derived Fungus Eutypella sp. F0219

Four previously undescribed polyketides, spiroeutypetides A–B ( 1 – 2 ), eutypetide I ( 3 ), and eutypetide J ( 4 ), were isolated from the rice culture of the marine-derived fungus Eutypella sp. F0219. Of these, compounds 1 – 3 possess unprecedented carbon skeletons, whereas 4 is a new polycyclic 10-membered lactone. The structures, including absolute configurations, were elucidated via spectroscopic data analysis, modified Mosher’s method, X-ray crystallography, GIAO 13 C NMR (DP4+) calculations, and ECD calculations. Spiroeutypetides A ( 1 ) and B ( 2 ) are two novel C 16 polyketides featuring distinct spirocyclization patterns, forming 5/6/5 and 6/6/5 tricyclic systems, respectively, whereas eutypetide I ( 3 ) is the first C 16 polyketide characterized by cleavage of the C4–C5 bond. All compounds were evaluated for their inhibitory effects on NO production in lipopolysaccharide-activated BV2 microglial cells. Eutypetide J ( 4 ) exhibited significant antineuroinflammatory activity by inhibiting microglial polarization and suppressing inflammasome-related proteins, including NLRP3 and caspase 1.