Sartorypyrone A

Most often, the structures of secondary metabolites are solved using a suite of NMR techniques. However, there are times when it can be challenging to position double bonds, particularly those that are fully substituted or when there are multiple double bonds in similar chemical environments. Ozone-induced dissociation mass spectrometry (OzID-MS) serves as an orthogonal structure elucidation tool, using predictable fragmentation patterns that are generated after ozonolysis across a carbon-carbon double bond. This technique is finding growing use in the lipidomics community, suggestive of its potential value for secondary metabolites. This methodology was evaluated by confirming the double-bond positions in five fungal secondary metabolites, specifically,ent-sartorypyrone E (1), sartorypyrone A (2), sorbicillin (3), trichodermic acid A (4), and AA03390 (5). This demonstrated its potential with a variety of chemotypes, ranging from polyketides to terpenoids and including those in both conjugated and nonconjugated polyenes. In addition, the potential of using this methodology in the context of a mixture was piloted by studyingAspergillus fischeri, first examining a traditional extract and then sampling a live fungal culturein situ. While the intensity of signals varied from pure compound to extract toin situ, the utility of the technique was preserved.

A new meroditerpene, sartorypyrone C (5), was isolated, together with the known tryptoquivalines L (1a), H (1b), F (1c), 3'-(4-oxoquinazolin-3-yl) spiro [1H-indole-3,5']-2,2'-dione (2) and 4(3H)-quinazolinone (3), from the culture of the marine sponge-associated fungus Neosartorya paulistensis (KUFC 7897), while reexamination of the fractions remaining from a previous study of the culture of the diseased coral-derived fungus N. laciniosa (KUFC 7896) led to isolation of a new tryptoquivaline derivative tryptoquivaline T (1d). Compounds 1a-d, 2, 3, and 5, together with aszonapyrones A (4a) and B (4b), chevalones B (6) and C (7a), sartorypyrones B (7b) and A (8), were tested for their antibacterial activity against four reference strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa), as well as the environmental multidrug-resistant isolates. Only aszonapyrone A (4a) and sartorypyrone A (8) exhibited significant antibacterial activity as well as synergism with antibiotics against the Gram-positive multidrug-resistant strains. Antibiofilm assays of aszonapyrone A (4a) and sartorypyrone A (8) showed that practically no biofilm was formed in the presence of their 2× MIC and MIC. However, the presence of a sub-inhibitory concentration of ½ MIC of 4a and 8 was found to increase the biofilm production in both reference strain and the multidrug-resistant isolates of S. aureus.