Aspersterols A-D, Ergostane-Type Sterols with an Unusual Unsaturated Side Chain from the Deep-Sea-Derived Fungus Aspergillus unguis

Abstract

Four previously undescribed ergostane-type sterols, aspersterols A-D (1-4), were isolated from a deep-sea-derived fungus, Aspergillus unguis IV17-109. The structures of the new compounds were determined by extensive analyses of their spectroscopic data, pyridine-induced deshielding effect, Mosher's method, and electronic circular dichroism calculations. The key feature of these sterols is the presence of a rare unsaturated side chain with conjugated double bonds at delta(17) and delta(22). The absolute configuration of C-24 in the side chain was determined by hydrogenation and comparing C-13 NMR chemical shifts of the hydrogenated products with literature values. In addition, aspersterol A (1) is the second representative of anthrasteroids with a hydroxy group at the C-2 position. Compound 1 showed cytotoxicity against six cancer cell lines, with GI50 values of 3.4 +/- 0.3 to 4.5 +/- 0.7 mu M, while 2-4 showed anti-inflammatory activity, with IC50 values ranging from 11.6 +/- 1.6 to 19.5 +/- 1.2 mu M.