Ilyomycins A − K, radicicol-type resorcylic acid lactones as potential immunosuppressants from a soil-derived Ilyonectria sp.

Abstract

Eleven previously undescribed radicicol-type resorcylic acid lactones (RALs), namely ilyomycins A − K (1–9, 10a and 10b), were isolated and identified from the fermented rice culture of a soil-derived fungus, Ilyonectria sp. (strain sb65). Their gross structures were determined by extensive spectroscopic data, and the absolute configurations were elucidated by single-crystal X-ray diffraction, the modified Mosher’s method, and Rh2(OCOCF3)4-induced electronic circular dichroism (ICD) experiment. Among them, 10a and 10b were a pair of inseparable regioisomers via intramolecular transacetylation. Compounds 3, 7, 8 and 10a/10b displayed immunosuppressive activities against T cell proliferation with IC50 values ranging from 1.2 to 21.7 μM, and against B cell proliferation with IC50 values ranging from 1.1 to 20.1 μM, which suggested that the α, β-unsaturated ketone from C-8 to C-10 was an important pharmacophore. Further study revealed that ilyomycin C (3) exerted anti-proliferative effect on T lymphocytes through Hsp90 inhibition.