Methyl Septanoside Hydrolysis as a Measure of Carbohydrate Ring Flexibility: Substrate Synthesis and Kinetics Analysis

A number of seven-membered ring systems have been found to have promising enzyme inhibiting properties. The common explanation for their efficacy is the apparent improved flexibility that the ring-system has over smaller rings. In an attempt to probe the validity of this hypothesis, unnatural seven-membered ring carbohydrates have been generated and subjected to kinetics analysis using hydrolysis. In particular, methyl α- and β-D-glycero-D-guloseptanoside were subjected to acid-catalyzed hydrolysis and monitored via HNMR experiments. The rate constants of the reactions were determined and compared to the hydrolysis rate constants of comparable pyranose carbohydrates and found to be significantly faster, indicating an increased flexibility in the seven-membered ring over smaller rings. Furthermore, when the α was compared with the β anomer, a reversal in the normal reactivity of glycosidic bond hydrolysis was found, with the α anomer being more reactive