Aculeatiols A–G: Lovastatin Derivatives Extracted from Aspergillus aculeatus

In this study, we isolated lovastatin derivatives, including aculeatiols A–G (1–7) and three known compounds (8–10), from Aspergillus aculeatus. Their structures and absolute configurations were experimentally determined by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and X-ray diffraction analyses, and the results were corroborated by quantum-chemical calculations. As members of the lovastatin derivatives, aculeatiols A–C (1–3) possess a γ-lactone functional group in the side chain. Compound 6 represents the first example that features an undescribed aromatized heterotetracyclic 6/6/6/6 ring system. Biologically, the lipid-lowering effects of all of these compounds were evaluated by analyzing the free fatty acid-induced intracellular lipid accumulation. In addition, compound 5, which regulated the transcription of genes associated with lipid uptake and synthesis, inhibited the accumulation of lipids.