Aspercyclide A–C, three novel fungal metabolites from Aspergillus sp. as inhibitors of high-affinity IgE receptor

Immunoglobin E (IgE) binds to the high-affinity IgE receptor on mast cells and basofils and causes release of inflammatory compounds that leads to allergic diseases. Inhibition of the ligand binding could lead to blockade of the release of inflammation causing compounds and thus alleviate asthma and other allergic diseases. Natural product screening and bioassay-guided isolation of an extract of Aspergillus sp. led to the identification of three novel 11-membered macrocyclic biphenyl ether lactones, aspercyclides A–C. Aspercyclide A inhibited the IgE binding with an IC50 of 200 μM. The isolation, structure elucidation, absolute stereochemistry, and the binding activities of these compounds are described.