NaBr-Induced Production of Brominated Azaphilones and Related Tricyclic Polyketides by the Marine-Derived Fungus Penicillium janthinellum HK1-6.

Cultivation of the mangrove rhizosphere soil-derived fungus Penicillium janthinellum HK1-6 with NaBr led to the isolation of two new brominated azaphilones, penicilones G and H (5, 6), two new tricyclic polyketides, penijanthinones A and B (7, 8), and two known azaphilones, penicilones A and B (1, 2). The planar structures and relative configurations of the new compounds were elucidated using comprehensive spectroscopic methods including 1D and 2D NOE spectra. Their absolute configurations were determined by chemical conversions, TDDFT ECD calculations, and comparisons of their ECD spectra. Interestingly, the NaBr-induced brominated azaphilones (5, 6) had the opposite configuration at C-7 compared to the chloro analogues (3, 4) produced by this fungus cultivated with sea salt. Ester hydrolysis of penicilone B (2) afforded the carboxylic acid side chain 2,4-dimethyldec-2-enoic acid (9), with a 4 S configuration assigned by its specific rotation. Penicilone H (6) showed antibacterial activity with MIC values ranging from 3.13 to 12.5 μg/mL.