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 (MIC 99 < 2.0 μM), including Mycobacterium tuberculosis H37Ra (MIC 99 = 0.9 μM).