General chemical synthesis of cyanidin-3-O-glycosides: configuration determination and structure-activity relationship analysis

Anthocyanins are a class of water-soluble flavonoid pigments widely distributed in plants, characterized by their flavylium cation core. Glycosylation modifications exert significant effects on the biological activities of anthocyanins with identical aglycones. This study accomplished the first chemical syntheses of cyanidin-3-O-galactoside (C3Gal) and cyanidin-3-O-arabinoside (C3Ara), providing a general glycosylation strategy. The configurations of β-D-galactopyranoside and α-L-arabinopyranoside were determined by 2D NMR. Comparative analysis of cyanidin-3-O-glucoside (C3Glu), C3Gal, and C3Ara revealed that C3Glu was the most stable, whereas C3Ara and C3Gal exhibited superior antioxidant activity. C3Ara also showed the strongest inhibition against α-amylase (IC 50  = 98.16 μM), consistent with molecular docking predictions. These results reveal the key structure-activity: hexoses (glucose, galactose) have higher stability and reduced activity. Pentosyl arabinosides have higher biological activity. This work provides a reliable preparation method and research direction for anthocyanin glycosides.