α‑Glucosidase Inhibitors via Green Pathway: Biotransformation for Bicoumarins Catalyzed by Momordica charantia Peroxidase

Peroxidase extracted from Momordica charantia catalyzed the H₂O₂-dependent oxidative coupling of 7-hydroxy-4-methylcoumarin to form four new dimers (1–4) and two known ones (5, 6). The structures, including the absolute configurations of axially chiral compounds, were unambiguously characterized by NMR spectroscopy, online HPLC-CD, and a variety of computational methods. Bioactive experiments demonstrated that compounds 1 and 2 had significant inhibitory effects on yeast α-glucosidase, much better than the controls. Noncompetitive binding mode was found by the graphical analysis of steady-state inhibition data. The mechanism of enzymatic inhibition confirmed in some depth that the inhibitors altered the secondary structure of α-glucosidase by decreasing the α-helix and increasing the β-sheet content. In summary, bicoumarins 1 and 2 might be exploited as the lead compounds for further research of antidiabetic agents, and this research provided a “green” method to synthesize compounds with the chiral biaryl axis generally calling for multistep reactions in organic chemistry.