Antibacterial Drimane Sesquiterpenes from Aspergillus ustus

Bioactivity-guided isolation of Aspergillus ustus led to the discovery of five new drimane sesquiterpenes, named ustusal A, ustusolate F and G, and ustusoic acid A and B, 1-5 respectively. Structural elucidation of these fungal terpenes relied on 1D and 2D NMR techniques, high-resolution mass spectrometry, and chiroptical properties. Their relative configurations were determined by NMR methods, while the absolute configurations were established using comparative analyses of computed and experimental NMR chemical shifts and ECD spectra. The sesquiterpenes exhibited weak activity against the clinically relevant pathogens vancomycin-resistant Enterococcus faecium and multidrug-resistant Staphylococcus aureus; however, the activity of 5 was drastically enhanced when equal amounts of stromemycin (6), a known metabolite coisolated from the same fraction from A. ustus, was added.