Reverse Anomeric Effects in Pyranose and Furanose Isomers in Schiff Bases of d-Galactosamine

The present study discloses for the first time furanose structures in imines derived from 2-amino-2-deoxyaldoses, thus assessing the anomeric equilibria. In DMSO solution, imines derived from d-galactosamine, [(2R,3R,4R,5R,6R)-3-amino-6-hydroxymethyltetrahydropyran-2,4,5-triol], exist in equilibrium between α and β anomers of the corresponding pyranose and furanose forms. In parallel analogy to glycoimines existing exclusively in pyranoid structures, β-anomers are extensively favored, a bias that can now be ascribed with confidence to a genuine reverse anomeric effect. Specifically, this effect describes a conformational preference opposite to the anomeric effect, thereby implying a destabilization of the axial anomer (α-anomer) together with pure steric effects. As extensively detailed throughout this paper by experimental and computational methods, the core argument is the existence, in both α-pyranose and α-furanose imines, of an intramolecular hydrogen bond between the anomeric hydroxyl and the nitrogen atom that inhibits the exo-anomeric effect. Moreover, solvation may synergistically reinforce this inhibition of the exo-anomeric effect, thus favoring the predominance of the β-anomer.