5’‐Methoxyarmillane, a Bioactive Sesquiterpenoid Aryl Ester from the Fungus Armillaria ostoyae

Higher fungi of the genus Armillaria belonging to the phylum Basidiomycota produce bioactive sesquiterpenoid aryl esters called melleolides. A bioactivity‐guided discovery process led to the identification of the new melleolide 5’‐methoxyarmillane (1) in organic extracts from the mycelium of Armillaria ostoyae. Remarkably, supplementation of rapeseed oil to the culture medium potato dextrose broth increased the production of 1 by a factor of six during the course of the 35 days fermentation. Compound 1 was isolated and its structure elucidated by UHPLC‐QTOF‐HR‐MS/MS and NMR spectroscopy. It showed toxicity against Madin‐Darby canine kidney II (MDCK II, IC50 19.2 μg/mL, 44.1 μM) and human lung cancer Calu‐3 cells (IC50 15.2 μg/mL, 34.9 μM) as well as moderate bioactivity against Mycobacterium tuberculosis (MIC 8 mg/mL, 18.4 μM) and Mycobacterium smegmatis (MIC 16 mg/mL, 36.8 μM), but not against Staphylococcus aureus, Escherichia coli, Candida albicans, and Septoria tritici. No inhibitory effects of 1 against the influenza viruses H3N2, H1N1pdm, B/Malaysia, and B/Massachusetts were observed. 5’‐Methoxyarmillane was isolated from cultures of Armillaria ostoyae in an optimized medium and the structure was elucidated by UHPLC‐QTOF‐HR‐MS/MS and NMR spectroscopy. It showed toxicity against Madin‐Darby canine kidney II and human lung cancer Calu‐3 cells as well as bioactivity against Mycobacterium tuberculosis and Mycobacterium smegmatis, but not against Staphylococcus aureus, Escherichia coli, Candida albicans, and Septoria tritici.