Cordycepsterols A-C, Anti-Inflammatory C₃₀ Ergosterols with a 6/6/6/5/6-Fused Ring System from Cordyceps militaris

Cordyceps militaris is a valuable edible and medicinal fungus. Its chemical composition and biological activity have become the focus of attention. In this study, three unusual C₃₀ ergosterols, cordycepsterols A-C (1-3), have been isolated from this fungus. Their structures have been identified according to extensive spectroscopic methods as well as computational quantum chemistry. They possess an unusual 6/6/6/5/6-fused pentacyclic system which might be derived from a normal ergosterol backbone by adding two skeletal carbons. Compounds 1-3 exhibit significant inhibitory activity against nitric oxide production with half maximal inhibitory concentration values of 3.0, 0.9, and 2.3 μM, respectively. They could significantly suppress the secretion of tumor necrosis factor-α and interleukin-6 at the concentration of 5 μM, which indicated that C. militaris and its cordycepsterols A-C have a potential anti-inflammatory application prospect.