Herbarumin Analogues from an Endophytic Isolate of Phoma sp. Isolated from a Seed of Bromus kalmia

During a study of a small collection of fungal endophytes found in prairie grasses, a culture of Phoma sp. (Endo 3417 = NRRL 54108) was isolated from a seed of Bromus kalmii obtained from a nursery in Winona, Minnesota. The ethyl acetate extract of solid-substrate fermentation cultures of this isolate showed antifungal activity against Fusarium verticillioides. Chemical studies of this extract led to isolation of three new polyketide metabolites that showed close NMR spectroscopic resemblance to members of the nonenolide class. Several nonenolides, including putaminoxin and herbarumins, have been reported as metabolites of Phoma spp. One of the new compounds is a simple analogue of the herbarumins. The other two contain a fused 6,6-ring system, but are clearly biosynthetically related. The structures of these metabolites were assigned based on analysis of 2D NMR and HRESIMS data. The relative configurations were established based on ¹H NMR coupling constants and NOESY data, while absolute configurations were assigned by ECD analysis of p-bromobenzoyl derivatives.