Phomaketals A and B,pentacyclic meroterpenoids from a eupC overexpressed mutant strain of Phoma sp.

Phomaketals A(1)and B(2),two tropolonic meroterpenoids with the unprecedented pentacyclic skeletons,were isolated from the solid-substrate fermentation cultures of a eupC overexpressed mutant strain of the fungus Phoma sp.,together with a biogenetically related secondary metabolite pughiinin B(3),and the known one noreupenifeldin B(4).The structures of 1–3 were elucidated primarily by nuclear magnetic resonance(NMR)experiments.The absolute configurations of 1 and 2 were assigned by electronic circular dichroism calculations and the calculated NMR with DP4+analysis,while that of 3 was established by single-crystal X-ray diffraction analysis using Cu Kαradiation.Biogenetically,phomaketals A(1)and B(2)could be derived from the hypothetical tropolonic sesquiterpene intermediates neosetophomone B(6)and 9-R-neosetophomone B(6),respectively,via different reactions cascades.Compound 1 showed antiproliferative effect only against the SUPB15 cells,with an 50%inhibitory concentration(IC50)value of 4.85μmol/L,while the co-isolated known meroterpenoid 4 displayed potent effects against three tumor cell lines,SUPB15,EL4,and H9,showing IC50values of 0.36–27.08μmol/L.