MDN-0057 to MDN-0060, a Family of Broad-Spectrum Antibiotics against Gram-Negative Pathogens Produced by Ophiosphaerella korrae

A novel family of antibiotics, MDN-0057 to MDN-0060 (1-4), was isolated from liquid cultures of the fungus Ophiosphaerella korrae. These compounds incorporate two isocyanide groups in their complex structures that were elucidated by extensive spectroscopic analyses, including HRESIMS, and 1D and 2D NMR experiments. The relative configurations were determined by using J-based configuration analyses and the interpretation of key NOESY correlations consistent with the existence of a major conformation in solution. Mosher ester derivatization analysis allowed the establishment of their absolute configurations. All four compounds displayed in vitro antibacterial activity with a broad spectrum against Gram-negative pathogens.