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

Peroxidase extracted from <i>Momordica charantia</i> catalyzed the H<sub>2</sub>O<sub>2</sub>-dependent oxidative coupling of 7-hydroxy-4-methylcoumarin to form four new dimers (<b>1</b>–<b>4</b>) and two known ones (<b>5</b>, <b>6</b>). 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 <b>1</b> and <b>2</b> 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 <b>1</b> and <b>2</b> 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.