AB-INITIO MOLECULAR-ORBITAL CALCULATION OF CARBOHYDRATE MODEL COMPOUNDS .5. ANOMERIC, EXOANOMERIC, AND REVERSE ANOMERIC EFFECTS IN C-GLYCOSYL, N-GLYCOSYL, AND S-GLYCOSYL COMPOUNDS

An ab initio study of the conformational behavior of alpha- and beta-a nomeric linkages in C-, N-, and S-glycosyl compounds has been carried out on axially and equatorially 2-substituted derivatives (2-ethyl, 2- methylamino, 2-thiomethyl, and 2-methylammonio) of tetrahydropyran as models. The geometry of the conformers about the anomeric C-X bond was determined by gradient optimization at the SCF level using the 6-31G basis set. The potential of rotation has been calculated using the 6- 31G and 6-31+G* basis sets. Vibrational frequencies were calculated a t the 6-31G level and used to evaluate zero-point energies, thermal e nergies, and entropies for minima. Variations in calculated valence ge ometries for the compounds, display structural changes distinctive for the anomeric and exo-anomeric effects. Differences between bond lengt hs and bond angles for different conformers correlate with the importa nce of the lone pair delocalization interactions. The calculated confo rmational equilibria have been used to estimate the magnitudes of the anomeric, reverse anomeric, and exo-anomeric effects. It was found tha t the anomeric effect decreases in the following order: chlorine > met hoxy similar to fluorine > thiomethyl > methylamino > ethyl > methylam monio, with the methylamino, ethyl, and methylammonio groups exhibitin g reverse anomeric effects. The sc preference of the methyl group over the ap orientation around the Cl-C bond in 2-ethyltetrahydropyran is assumed to be entirely on basis of steric interactions. The exo-anomer ic effect is expected to be present when the preference for the sc con formation is larger than that for the ethyl group. Thus, the exo-anome ric effect decreases in the order methoxy similar to methylamino > thi omethyl. The methylammonio group does not show an exo-anomeric effect.