Orientations of carbohydrate substituents

Abstract

Once a specific hydrogen bond forms between a carbohydrate and a receptor, the torsional freedom about the OC bond must be mostly “frozen out”. The orientation of the hydroxyl group of an aglycone in a glycosylation reaction is also known to affect its reactivity. In order to assess the range of these effects, all 81 combinations of staggered hydroxyl rotamers of α- l-fucose were studied using the AM1 semi-empirical method. These 81 conformers were reduced to 26 after energy minimization, with a total range of energies of 8.5 kcal mol −1. Fifty selected hydroxyl rotamers of the disaccharide Man(β1,4)GlcNAc(β1,O)Me were also examined by AM1 calculations using a procedure which minimizes the importance of intramolecular H bonding. A range of ± 4.0 kcal mol −1 was found for 11 hydroxyl rotamers with the lowest energy glycosidic linkage conformation ( φ H = 62.2 ° ± 2.4 °, ψ H = − 3.2 ° ± 3.0 °). This study leads to the practical question of selecting the appropriate hydroxyl rotamer for carbohydrate computer libraries.