Kinetics and mechanism of hydrolysis of 1-(2'-acetoxybenzoyl)-2-deoxy-alpha-D-glucopyranose, a novel aspirin prodrug.

Abstract

The formation rate of aspirin from the prodrug was determined as a function of the pH, temperature, and dielectric constant of the solvent spectrophotometrically and was confirmed by high-pressure liquid chromatography. Aspirin formation was first order with respect to the prodrug and zero order with respect to the hydroxide-ion concentrations. The hydrolysis rate was independent of buffer concentration but very sensitive to the dielectric constant of the solvents. The half-life for the formation of aspirin at 37 degrees was 7 min. The activation energy for the hydrolysis was 23.7 kcal/mole. The results suggest that the hydrolysis of the prodrug to aspirin proceeds by an SN1-type mechanism.