α-Glucosidase Inhibitors From the Coral-Associated Fungus Aspergillus terreus

Nine novel butenolide derivatives, including four pairs of enantiomers, named (+/-)-asperteretones A-D (1a/1b-4a/4b), and a racemate, named asperteretone E (5), were isolated and identified from the coral-associated fungus Aspergillus terreus. All the structures were established based on extensive spectroscopic analyses, including HRESIMS and NMR data. The chiral chromatography analyses allowed the separation of (+/-)-asperteretones A-D, whose absolute configurations were further confirmed by experimental and calculated electronic circular dichroism (ECD) analysis. Structurally, compounds 2-5 represented the first examples of prenylated gamma-butenolides bearing 2-phenyl-3-benzyl-4H-furan-1-one motifs, and their crucial biogenetically related metabolite, compound 1, was uniquely defined by an unexpected cleavage of oxygen bridge between C-1 and C-4. Importantly, (+/-)-asperteretal D and (4S)-4-decarboxylflavipesolide C were revised to (+/-)-asperteretones B (2a/2b) and D (4), respectively. Additionally, compounds 1a/1b-4a/4b and 5 were evaluated for the alpha-glucosidase inhibitory activity, and all these compounds exhibited potent inhibitory potency against alpha-glucosidase, with IC50 values ranging from 15.7 +/- 1.1 to 53.1 +/- 1.4 mu M, which was much lower than that of the positive control acarbose (IC50 = 154.7 +/- 8.1 mu M), endowing them as promising leading molecules for the discovery of new a-glucosidase inhibitors for type-2 diabetes mellitus treatment.