Exploration of conformational flexibility and hydrogen bonding of xylosides in different solvents, as a model system...

The predominantly populated conformation of carbohydrates in solution does not necessarily represent the biologically active species; rather, any conformer accessible without too large an energy penalty may be present in a biological pathway. Thus, the conformational preferences of a naphthyl xyloside, which initiates in vivo synthesis of antiproliferative glycosaminoglycans, have been studied by using NMR spectroscopy in a variety of solvents. Equilibria comprising the conformations (4)C1, (2)SO and (1)C4 were found, with a strong dependence on the hydrogen bonding ability of the solvent. Studies of fluorinated analogues revealed a direct hydrogen bond from the hydroxyl group at C2 to the fluorine atom at C4 by a (1h)JF4,HO2 coupling. Hydrogen bond directionality was further established via comparisons of fluorinated levoglucosan molecules.