New Austalides from the Sponge‐Associated Fungus Aspergillus sp.

Abstract Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium , yielded five new meroterpenoid metabolites, austalides M–Q ( 1 – 5 ), together with nine known compounds ( 6 – 13 ). The structures of the new compounds were unambiguously elucidated on the basis of extensive 1D and 2D NMR methods and by mass spectral analysis. Furthermore, the absolute configurations of 1 and 4 were determined by time‐dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations, allowing the assignment of the absolute configuration of analogous compounds 2 , 3 , and 5 . The calculations revealed that the conformation of the benzene‐fused phthalide chromophore, which is sensitive to even minor changes in its proximity, is decisive for the ECD parameters, rendering a simple ECD comparison of related homochiral austalides difficult. All compounds were evaluated for their cytotoxic activity against murine cancer cell line L5178Y by using the MTT method. Compounds 8 and 11 exhibited moderate to pronounced cytotoxicity, with IC 50 values of 39.4 and 0.2 μ M , respectively, whereas the remaining investigated compounds showed either weak or no activity in this assay.