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

In our efforts toward the development of enzyme-like catalysts for regiosel ective functionalization of unprotected sugars, DMAP-catalyzed acetylation of unprotected carbohydrates in chloroform was investigated. Product distri butions of monoacetylated sugars were determined under kinetic control. To accurately evaluate the relative reactivity of each OH group, reaction cond itions were used under which only monoacetylated sugars were obtained and a lmost no diacetylated sugars were formed as by-products. Systematic acetyla tion experiments of glucose, mannose, and galactose revealed the decisive r ole of intramolecular hydrogen-bonding networks among carbohydrate OH group s. The relative reactivities in the DMAP-catalyzed acetylation were success fully correlated with the calculated proton affinity of each OH group in ca rbohydrates.