Aculeatiols A-G: Lovastatin Derivatives Extracted from Aspergillus aculeatus.

Abstract

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.