Phase-dependent antioxidant behavior in a synthetic C-α-glucogallin analogue library by photoredox-mediated α-ketonylation.

Abstract

Phenolic acid glycosyl esters like glucogallins are promising antioxidants but are often limited by hydrolytically labile O-glycosidic linkages. Here, twelve C-α-glucogallin analogues were synthesized in six steps from commercial peracylated sugars by combining four monosaccharides with three plant-derived phenolic acids. Photoredox-enabled C-α-ketonylation furnished C-ketonyl sugars in 70-88% yield with high α-selectivity and aqueous stability over 120 h. Chemical and food-relevant antioxidant assays identified the protocatechuic acid derivatives 4ac-dc as the most active subset (70-99% activity) with marked phase-dependent sugar effects. Specifically, the most hydrophilic glucoside 4ac performed best in aqueous systems yet remained less active than VC, whereas the less polar rhamnoside 4dc was most effective in lipophilic models, with activity exceeding BHT, as indicated by a 2.1-fold lower IC50 in the lipid peroxidation assay and greater protection against canola oil oxidation at 120 °C. Collectively, these findings highlight C-α-glucogallins as structurally tunable and highly effective antioxidants for lipid-rich foods.