A MODEL GLYCOSIDIC LINKAGE - AN AB-INITIO GEOMETRY OPTIMIZATION STUDYOF 2-CYCLOHEXOXYTETRAHYDROPYRAN

Quantum mechanical ab initio calculations have been performed to study regions close to minimum energy conformations of a pseudo-disaccharid e, viz., 2-cyclohexoxytetrahydropyran. Dunning's double-zeta basis set was used for most of the calculations. The global minimum was obtaine d for the axial conformer, and a local minimum for the axial form was also observed at 0.5 kcal/mol above the global minimum. The equatorial form showed local energy minima for two conformers about 2.5 kcal/mol above the global minimum. Analysis of the effect of electron correlat ion on the geometry optimization was also performed on the MP2 level o f approximation using the DZ basis set. Geometry optimization calculat ions at various values of the psi dihedral angle were performed with t he phi dihedral angle restrained to the staggered conformation where t he exoanomeric effect is contributing to energy stabilization. Barrier heights between the axial conformers and between the equatorial confo rmers, respectively, were well below kT at room temperature as identif ied from the ab initio calculations, thus indicating a conformationall y averaged low-energy region. The barrier for the full rotation of the psi dihedral angle is estimated to be ca 4-5 kcal/mol. The relative e nergies and the geometries obtained from the calculations at the Hartr ee-Fock level of approximation were compared to those from MM3 calcula tions. The optimal conformations calculated with the ab initio and MM3 methods, respectively, were similar for the global minimum, whereas s ignificant differences were observed for the phi and psi dihedral angl es as well as in relative energies for low-energy conformers. The valu es of the psi dihedral angle in the optimal geometries were closer tog ether when calculated by the ab initio method than obtained from MM3 c alculations, thus indicating a more narrow low-energy region.