Stereochemical preference of nucleophillic cleavage in methyl erythrofuranosides explained by density functional theory computations

The nucleophillic substitution is a common method for preparation of saccharide derivatives. For biologically active compounds, it is desirable that the stereochemistry is under control and the amount of byproducts is limited. Therefore, we studied the SN2 nucleophillic attacks of the azide anion on methyl 2,3-anhydro-α- and -β-l-erythrofuranoside, as well as on their epithio and epimino analogues, which are used as common intermediates in sugar chemistry. Geometry and energetics of the reactions were investigated in the gas phase and in two different solvents using the density functional theory methods. Equilibrium structures of the reactants, reaction-complexes, transition states and products were localized on the computed potential energy surfaces. According to the theory the methoxy group may suppress the substitutions at the 2-position, but detailed reaction rate is influenced by nature of the furanosides and the presence of solvent. Predicted substitution selectivity in the position 2 or 3 of the furanose sugars is in agreement with experimental data.