Polyketide Skeletons from the Marine Alga-Derived Fungus Coniothyrium cereale

The fungus Coniothyrium cereale was isolated from the Baltic Sea alga Enteromorpha sp. Upon cultivation in saline medium, C. cereale produced the structurally unprecedented isoindole pseudoalkaloid conioimide (1) and the polyketide cereoanhydride (2). Because of the very limited amount of compounds isolated, the structures of 1 and 2 were established from extensive NMR spectroscopic and mass spectrometric analyses, and in the case of 1, the structural analysis was completed by NMR shielding calculations. Conioimide and cereoanhydride represent new structural types of polyketides. Experiments with 13C-labeled acetate proved the polyketide nature of the major and known C. cereale metabolite ()-trypethelone (3), which is proposed to be the precursor of cereoanhydride. Conioimide has prominent and selective inhibitory activity towards the protease human leukocyte elastase (HLE), an enzyme involved in many inflammatory diseases, with an IC50 (half maximal inhibitory concentration) value of 0.2 mu g?mL1.