Asteltoxins I-T: Polyketides from a Plant Endophytic Strain of Pochonia bulbillosa.

Asteltoxins I-T (1-12), 12 asteltoxin-type polyketides, together with four known analogues (13-16), were isolated from an endophytic fungus Pochonia bulbillosa KNI755. Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 1 featured a tetrahydro-2H-pyran-linked asteltoxin heterodimer incorporating a clavatol unit. Compounds 2 and 3 demonstrated unique tetrahydro-1,4-oxazine-linked asteltoxin heterodimers comprising a diphenyl ether unit. Compounds 4-7 presented unusual 1,4-dioxane-linked asteltoxin heterodimers also containing a diphenyl ether unit. Compounds 1-7 were immunosuppressive against concanavalin A (ConA)-induced T cell proliferation and lipopolysaccharide (LPS)-induced B cell proliferation with EC50 values ranging from 9.2 to 26 μM and from 6.3 to 27 μM, respectively. Compound 1 exhibited inhibitory activity against the HCT116 human cancer cell line with an IC50 value of 10 μM.