Synthesis and Comparative Structure-Activity Study of Carbohydrate-Based Phenolic Compounds as α-Glucosidase Inhibitors and Antioxidants

Twenty-one natural and unnatural phenolic compounds containing a carbohydrate moiety were synthesized and their structure-activity relationship (SAR) was evaluated for alpha-glucosidase inhibition and antioxidative activity. Varying the position of the galloyl unit on the 1,5-anhydro-D-glucitol (1,5-AG) core resulted in changes in the alpha-glucosidase inhibitory activity and notably, particularly strong activity was demonstrated when the galloyl unit was present at the C-2 position. Furthermore, increasing the number of the galloyl units significantly affected the alpha-glucosidase inhibition, and 2,3,4,6-tetra-galloyl-1,5-AG (54) and 2,3,4,6-tetra-galloyl-D-glucopyranose (61) exhibited excellent activities, which were more than 13-fold higher than the alpha-glucosidase inhibitory activity of acertannin (37). Moreover, a comparative structure-activity study suggested that a hemiacetal hydroxyl functionality in the carbohydrate core and a biaryl bond of the 4,6-O-hexahydroxydiphenoyl (HHDP) group, which are components of ellagitannins including tellimagrandin I, are not necessary for the alpha-glucosidase inhibitory activity. Lastly, the antioxidant activity increased proportionally with the number of galloyl units.