Phenazinoates A‒E, five pairs of phenazine conjugates from a mangrove soil-derived Streptomyces strain OUCMDZ-4923

Phenazinoates A-E (1-5), comprising five pairs of methyl saphenate conjugates with genistein, o-aminophenol, p-acetaminophenol and glycerol, were isolated from the fermentation broth of mangrove soil-derived Streptomyces sp. OUCMDZ-4923. Their structures were determined through comprehensive one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, coupled with high-resolution electrospray ionization mass spectrometry. The absolute configurations of each isomer were established by comparing experimental electronic circular dichroism spectra with calculated counterparts. Based on the biosynthetic pathway analysis, compounds 1‒3 were semi-synthesized from the reactions of methyl (R)-saphenate with genistein, o-aminophenol, and o-formamidophenol, utilizing microwave-assisted solid acid catalysis. The compounds were resolved as enantiomerically pure forms and subsequently tested for antibacterial efficacy against six pathogenic bacteria. Phenazinoates A (1) and B (2) demonstrated bioactivity against four Gram-positive bacterial strains, with minimum inhibitory concentration values ranging from 0.78 to 3.13 μg/mL.