AB-INITIO MOLECULAR-ORBITAL CALCULATION OF CARBOHYDRATE MODEL COMPOUNDS .2. CONFORMATIONAL-ANALYSIS OF AXIAL AND EQUATORIAL 2-METHOXYTETRAHYDROPYRANS

An ab initio study of the conformational behavior of alpha- and beta-g lycosidic linkages has been carried out on axial and equatorial 2-meth oxytetrahydropyrans as models. The geometry of the conformers about th e glycosidic C-O bond was determined by gradient optimization at the S CF level using the 4-21G and 6-31G basis sets and at the second-order Moller-Plesset level using the MP2/6-31G basis set. The potential of rotation has been calculated using 4-21G, 6-31G, 6-31+G*, MP2/6-31G* , and 6-311++G* basis sets. At all levels of theory, both axial and e quatorial forms prefer the GT conformation around the C-O glycosidic b ond. Conformational changes in bond lengths and angles at the anomeric center also display significant variations with computational methods , but structural trends ate in fair agreement with experiment. The cor rection for the effect of zero-point energy, thermal energy, and entro py on the axial-equatorial energy difference at the 6-31G level is -0 .63 kcal/mol. After these corrections to the energy difference calcula ted at the 6-31G level, the axial form is favored by 0.84 kcal/mol, i n reasonable agreement with experimental values of Delta G = 0.7-0.9 k cal/mol estimated for nonpolar solvents. Solvent effects reduce this e nergy difference; in the extreme case of water, a value of 0.24 kcal/m ol was obtained. Complete torsional profiles have been obtained for ro tation about the glycosidic C-O bond in eleven solvents, and the calcu lated energy differences are in fair agreement with experimental data on 2-alkoxytetrahydropyrans in solutions. The MM3 (epsilon = 1.5) forc e field reproduces the 6-31G ab initio energy difference reasonably w ell, but barrier heights are in poor agreement with the ab initio data . The calculated energies and geometries provide an essential set of d ata for the parametrization of the behavior of acetal fragments in mol ecular mechanical force fields for carbohydrates.