Ravidomycin Analogs from Streptomyces sp. Exhibit Altered Antimicrobial and Cytotoxic Selectivity.

Six new ravidomycin analogs ( 1 - 4 , 6 , and 7 ) were isolated from Streptomyces sp. Am59 using UV- and LCMS-guided separation based on Global Natural Products Social (GNPS) molecular networking analysis. Furthermore, we isolated fucomycin V ( 9 ), which possesses the same chromophore as ravidomycin but features a d-fucopyranose instead of d-ravidosamine. This is the first report of 9 as a natural product. Four new analogs ( 10 - 13 ) of 9 were also isolated. The structures were elucidated by combined spectroscopic and computational methods. We also found an inconsistency with the published [α] D 25 of deacetylravidomycin, which is reported to have a (-) sign. Instead, we observed a (+) specific rotation for the reported absolute configuration of deacetylravidomycin (containing d-ravidosamine). We confirmed the positive sign by reisolating deacetylravidomycin from S. ravidus and by deacetylating ravidomycin. Finally, antibacterial, antifungal, and cytotoxicity activities were determined for the compounds. Compared to deacetylravidomycin, the compounds 4 - 6 , 9 , 11 , and 12 exhibited greater antibacterial selectivity.