New immunosuppressive secondary metabolites from the endophytic fungus Aspergillus sp.

Six new metabolites, including two diphenolic derivatives (1 and 2), one pseurotin (3), one butenolide derivative (4), one benzopyran (5) and one isochromane lactone (6), together with ten known compounds (7-16) were isolated from an endophytic fungus Aspergillus sp. Their planar structures and absolute configurations were established based on techniques of MS, NMR, IR, UV, [Rh2(OCOCF3)4] complex-induced ECD, quantum chemical electronic circular dichroism (ECD) calculations, and single crystal X-ray diffraction. Structurally, compound 2 represents the first example of diphenolic derivative possessing an unusual 1-oxaspiro[2.4]heptane core bearing a 5/3 bicyclic skeleton; compound 3 represents the first example of pseurotin type natural products that only one hydroxy group is substituted at side chain. In bioassay, compounds 3, 7 and 8 exhibited potential inhibitory effect on the proliferation of anti-CD3/anti-CD28 monoclonal antibodies (mAbs) induced murine T cells, with IC50 values of (7.81 +/- 0.71), (8.25 +/- 0.78) and (8.84 +/- 0.81) mu M, respectively.

Automated summary

Six new metabolites were isolated from an endophytic fungus Aspergillus sp., with compound 2 being the first example of a diphenolic derivative with an unusual structure, and compound 3 being the first example of a pseurotin type natural product with only one hydroxy group substituted on the side chain. Compounds 3, 7, and 8 exhibited inhibitory effects on murine T cell proliferation induced by anti-CD3/anti-CD28 monoclonal antibodies.