Lincolnenins A–D: Isomeric Bactericidal Bianthracenes from Streptomyces lincolnensis

Cultivation profiling followed by chemical analysis of Streptomyces lincolnensisyielded 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 1–4on the basis of diagnostic ROESY correlations and ECD calculations, whereas acid-mediated dehydration of 1led to formation and revision of the absolute configuration of the biosynthetically related known Streptomycesantibiotic, setomimycin (5). Lincolnenin A (1) exhibited significant bactericidal activity against multiple susceptible and drug-resistant Gram-positive pathogens (MIC99< 2.0 μM), including Mycobacterium tuberculosisH37Ra (MIC99= 0.9 μM).