Undescribed indanomycin derivatives from ΔidmH mutant of Streptomyces antibioticus

Indanomycin represents a structurally distinctive polyether ionophore antibiotic featuring a pyrroloketoindane scaffold. The indane ring system, rare among natural products, is postulated to form through an enzymatic Diels-Alder cyclization. To obtain further knowledge of indanomycin biosynthesis, we chemically re-investigated the ΔidmH mutant of Streptomyces antibioticus. This led to the discovery of four new indanomycin derivatives, designated as indanomycins B - E. Their structures and absolute configurations were characterized through extensive spectroscopic methods, ¹³C NMR calculation with DP4+ probability analysis, and TDDFT/ECD calculations. Structurally, indanomycins B - D possess a linear tetraene structure, while indanomycin E is identified as a diastereoisomer of indanomycin with distinct indane configuration. These findings expand the structural diversity of indanomycins. The co-occurrence of indanomycin and indanomycin E, both as endo-type Diels-Alder adducts, suggests the possibility of spontaneous intramolecular [4 + 2] cycloadditions. Biological evaluation revealed potent antibacterial activity against Gram-positive pathogens, highlighting the importance of indane core. Coupled with acceptable toxicity profiles, these compounds demonstrate potential for development as anti-infective agents.