Antibacterial polyketides and ascochlorins from deep-sea cold-seep-derived fungus Furcasterigmium furcatum (syn. Acremonium furcatum)

Three new secondary metabolites, including a new polyketide, acrefurcatone A (1), a new ascochlorin analogue, acremochlorin N (2), and 3-phenylcyclopentane-1,2-diol (±-3), a pair of new naturally occurring enantiomers, along with nine known ascochlorins (4–12), were identified from Furcasterigmium furcatum CS-280 (syn. Acremonium furcatum CS-280), a fungus isolated from the deep-sea cold-seep sediment samples collected in the South China Sea. Their structures were determined by detailed interpretation of NMR spectroscopic and mass spectrometric data. The relative configurations of compounds 1–3 were assigned by NOESY correlations combined with gauge-independent atomic orbital (GIAO) NMR shift calculations and DP4+ probability analysis, while their absolute configurations were assigned by time-dependent density functional (TDDFT) ECD calculations and specific rotation calculations. Compound 1 exhibited potent activity against the human pathogenic bacterium Pseudomonas aeruginosa, with a minimum inhibitory concentration (MIC) value of 8 μg/mL. The isolated ascochlorins also showed potent activities against aquatic bacteria, especially for Vibrio harveyi and V. alginolyticus, with MIC values comparable to chloramphenicol. Analysis of the structure-activity relationship indicated that the cinnamate derivative, such as compound 1, or the presence of chlorine atom in ascochlorin derivatives, such as compounds 4, 6, and 7, significantly enhanced the antibacterial activities. This is the first report of anti-Vibrio activities for ascochlorin derivatives.