Lincolnenins A-D: Isomeric Bactericidal Bianthracenes from Streptomyces lincolnensis.

Cultivation profiling followed by chemical analysis of Streptomyces lincolnensis yielded four new isomeric bianthracenes, lincolnenins A-D (1-4), with relative stereostructures assigned on the basis of detailed spectroscopic analysis. Lincolnenins A (1) and B (2) exhibit restricted rotation about alternate bianthracene 9-9' and 9-8' bridges, respectively, and exist as single atropisomers, whereas C (3) and D (4) are thermally interconvertible atropisomers sharing a common 8-8' bianthracene bridge. Absolute configurations were assigned to 1-4 on the basis of diagnostic ROESY correlations and ECD calculations, whereas acid-mediated dehydration of 1 led to formation and revision of the absolute configuration of the biosynthetically related known Streptomyces antibiotic, setomimycin (5). Lincolnenin A (1) exhibited significant bactericidal activity against multiple susceptible and drug-resistant Gram-positive pathogens (MIC99 < 2.0 μM), including Mycobacterium tuberculosis H37Ra (MIC99 = 0.9 μM).