Antimicrobial specialized metabolites from the marine coral-derived fungus Talaromyces variabilis

Specialized metabolites derived from marine-derived fungi are an important source of lead compounds. In the current study, four previously undescribed aromatic polyketides, named talavariabones A-D (1-4), two previously undescribed alkaloids, named talavariabones E-F (5-6), along with two known metabolites (7-8) were isolated and identified from the coral-derived fungus Talaromyces variabilis. Their structures and absolute configurations were elucidated based on extensive spectroscopic analysis, comparison with the literature data, X-ray diffraction, and TDDFT-ECD calculations. Structurally, compound 1, a polyketide featuring a 5/6-spirocyclic framework decorated with two tert-butyl groups, represents an unprecedented skeleton in natural products. Compounds 2, 3, 5 and 6 are the rare chlorine-substituted natural products, expanding the chemical diversity of halogenated metabolites from microbial sources. Compounds 2a, 2b, 3, 5 and 7 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis with MIC values ranging from 8.0 to 32.0 μg/mL.