Effect of intramolecular hydrogen-bonding network on the relative reactivities of carbohydrate OH groups†

Abstract

In our efforts toward the development of enzyme-like catalysts for regioselective functionalization of unprotected sugars, DMAP-catalyzed acetylation of unprotected carbohydrates in chloroform was investigated. Product distributions of monoacetylated sugars were determined under kinetic control. To accurately evaluate the relative reactivity of each OH group, reaction conditions were used under which only monoacetylated sugars were obtained and almost no diacetylated sugars were formed as by-products. Systematic acetylation experiments of glucose, mannose, and galactose revealed the decisive role of intramolecular hydrogen-bonding networks among carbohydrate OH groups. The relative reactivities in the DMAP-catalyzed acetylation were successfully correlated with the calculated proton affinity of each OH group in carbohydrates.