Resorcylic acid lactone derivatives with immunosuppressive activity from the endophytic Podospora sp. G214.

Nine previously unreported resorcylic acid lactone derivatives (1-6, 7a, 8a and 8b), together with three known analogues (7b, 9, 10), were isolated and identified from the solid rice-based culture of Podospora sp. G214. Their structures with absolute configurations were determined by extensive spectroscopic data analysis, electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Compounds 1-6 are rare naturally occurring oxidative degradation products of RALs, for which a plausible biosynthetic pathway was proposed. Compound 1 exhibited immunosuppressive activity on concanavalin A-induced T cell proliferation, with an IC50 value of 12.2 μM, as well as on lipopolysaccharide-induced B cell proliferation, with an IC50 value of 8.4 μM. Compounds 2, 8a and 8b showed modest immunosuppressive activity, with IC50 values ranging from 22.2 to 40.9 μM.