Bulbiferates A and B: Antibacterial Acetamidohydroxybenzoates from a Marine Proteobacterium, Microbulbifer sp.

Here we report the discovery of two new 3-acetamido-4-hydroxybenzoate esters, bulbiferates A (1) and B (2), isolated from Microbulbifer sp. cultivated from the marine tunicate Ecteinascidia turbinata. The structures of 1 and 2 were determined by analysis of 2D NMR and MS data. Additionally, three synthetic analogues (3-5), differing in ester sizes/lengths, were prepared for the purposes of evaluating potential structure-activity relationships; no clear correlations tying ester lengths to activity were evident. Bulbiferates A (1) and B (2) demonstrated antibacterial activity against both Escherichia coli (E. coli) and methicillin-sensitive Staphylococcus aureus (MSSA), whereas the synthetic analogues 3 and 4 displayed activity only against MSSA.

Anti-Cryptococcus Phenalenones and Cyclic Tetrapeptides from Auxarthron pseudauxarthron.

Auxarthrones A-E (1-5), five new phenalenones, and two new naturally occurring cyclic tetrapeptides, auxarthrides A (7) and B (8), were obtained from three different solvent extracts of cultures of the coprophilous fungus Auxarthron pseudauxarthron. Auxarthrones C (3) and E (5) possess an unusual 7a,8-dihydrocyclopenta[a]phenalene-7,9-dione ring system that has not been previously observed in natural products. Formation of 1-5 was found to be dependent on the solvent used for culture extraction. The structures of these new compounds were elucidated primarily by analysis of NMR and MS data. Auxarthrone A (1) was obtained as a mixture of chromatographically inseparable racemic diastereomers (1a and 1b) that cocrystallized, enabling confirmation of their structures by X-ray crystallography. The absolute configurations of 7 and 8 were assigned by analysis of their acid hydrolysates using Marfey's method. Compound 1 displayed moderate antifungal activity against Cryptococcus neoformans and Candida albicans, but did not affect human cancer cell lines.

Benzophenone and Fimetarone Derivatives from the Coprophilous Fungus Delitschia confertaspora.

Studies of the genome-sequenced, flutimide-producing coprophilous fungus Delitschia confertaspora (ATCC 74209), originally obtained from a sample of rock hyrax (Procavia capensis) dung collected in Namibia, led to the discovery of three new highly aromatic natural products named delicoferones A-B (1-2) and fimetarone B (3). The new benzophenone derivatives 1 and 2 have a somewhat unusual skeleton that incorporates three aromatic rings linked via two ketone carbonyl groups, while 3 contains a spiro[chroman-3,7'-isochromene]-4,6'(8'H) skeleton reported only once previously. The structures of these compounds were assigned mainly by analysis of 2D NMR and HRESITOFMS data.

Hypocoprins A-C: new sesquiterpenoids from the coprophilous fungus Hypocopra rostrata.

Studies of the coprophilous fungus Hypocopra rostrata (TTI-0009, NRRL 66178) isolated from a sample of horse dung collected in Texas led to the isolation of three new sesquiterpenoids that we named hypocoprins A-C (1-3), together with the known fungal metabolite helvolic acid. The new metabolites have a distinctive ring system consisting of fused cyclopropane and cyclodecene units not previously reported from a fungal source. Compounds 1 and 3 moderately inhibited growth of Staphylococcus aureus. The structures of these metabolites were assigned mainly by analysis of 2D NMR and HRESITOFMS data. Relative and absolute configurations were assigned by interpretation of NMR J-values and NOESY data and by application of Mosher's method. These results represent the first report of chemistry from any strain of the genus Hypocopra.

Dhilirolides A-D, meroterpenoids produced in culture by the fruit-infecting fungus Penicillium purpurogenum collected in Sri Lanka.

Dhilirolides A (1) to D (4), a family of secondary metabolites with a putative meroterpenoid biogenetic origin and the unprecedented dhilirane and isodhilirane carbon skeletons, have been isolated from laboratory cultures of the fruit-infecting fungus Penicillium purpurogenum collected in Sri Lanka. The structures of 1 to 4 were elucidated by interpretation of NMR data and a single crystal X-ray diffraction analysis of 1.