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 13C NMR (DP4+) calculations, and ECD calculations. Spiroeutypetides A (1) and B (2) are two novel C16 polyketides featuring distinct spirocyclization patterns, forming 5/6/5 and 6/6/5 tricyclic systems, respectively, whereas eutypetide I (3) is the first C16 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.
Huang et al. (2026) studied this question.