AB-INITIO MOLECULAR-ORBITAL CALCULATION OF CARBOHYDRATE MODEL COMPOUNDS .6. THE GAUCHE EFFECT AND CONFORMATIONS OF THE HYDROXYMETHYL AND METHOXYMETHYL GROUPS

Conformational properties and the gauche effect of the two functional groups, hydroxymethyl and methoxymethyl, in hexopyranosides have been studied with nb initio methods using the methyl 2,3,4-trideoxy-alpha-D -glycero-hexopyranoside (1), methyl 2,3,4-trideoxy-beta-D-glycero-hexo pyranoside (2), methyl thyl-2,3,4-trideoxy-alpha-D-glycero-hexopyranos ide (3), and methyl ethyl-2,3,4-trideoxy-beta-D-glycero-hexopyranoside (4) as models. The geometry of the conformers around the C5-C6 bond f or the methyl 2,3,4-trideoxy-D-glycero-hexopyranosides was determined by gradient optimization at the SCF level using the 6-31G, 6-31+G*, a nd 6-311++G* basis sets. The optimized geometries were used to calcul ate the energy of the gauche-trans (gt), trans-gauche (tg), and gauche -gauche (gg) conformers with the 6-31G:, 6-31+G* 6-31fG**, 6-31G**, 6 -311G, and 6-311++G** basis sets, Electron correlation effects were a ccounted for at the second-order Moller-Plesset perturbation (MP2) lev el using the 6-31G basis set and using the adiabatic connection metho d (ACM) of density functional theory (DFT) using standard 6-31G, dzvp , and cc-pvtz basis sets. Solvent effects on the stability of conforme rs were evaluated using a continuum model. At all levels of theory, 1 and 2 prefer the gauche over the trans conformers around the C5-C6 bon d. This preference is due to internal hydrogen bonding which is possib le in the gg(sc) and gt(-sc) conformers. Solvent effects decrease this preference by similar to 0.9 kcal/mol. Methylation of the oxygen of t he C6 hydroxyl completely reversed the relative energy of conformers, such that in 3 and 4, the trans conformer is favored. The trans prefer ence is decreased by solvent which stabilized the gauche conformers by 0.7-1.3 kcal/mol with respect to the trans. These results suggest tha t the gauche preference of the hydroxymethyl group in 1 and 2, is due to the presence of hydrogen bonding and not due to the gauche effect.