Chlorogenic Acid Derivatives with Alkyl Chains of Different Lengths and Orientations: Potent α-Glucosidase Inhibitors.

α-Glucosidases play important roles in the digestion of carbohydrates and biosynthesis of viral envelope glycoproteins. Inhibitors of α-glucosidase are promising candidates for the development of antitype II diabetics and anti-AIDS drugs. Here, we report the synthesis and α-glucosidase inhibitory activity of mono- and diketal/acetal derivatives of chlorogenic acid. The diketal derivatives showed more potent inhibitory activity than the monoketals. The 1,7-(5-nonanone) 3,4-(5-nonanone)-chlorogenic acid diketal showed remarkable inhibitory activity against α-glucosidases with potency better than that of 1-deoxynojirimycin hydrochloride. Four diasteremers of pelargonaldehyde diacetal and two of monoacetal derivatives of chlorogenic acid were synthesized in this study. They showed significant potent inhibition similar to or more potent than the ketal counterparts. Acetals with the alkyl chain oriented toward position 2 of chlorogenic acid showed more potent activity than those oriented toward position 6. [ABSTRACT FROM AUTHOR]