CONFORMATIONAL-ANALYSIS OF TREHALOSE DISACCHARIDES AND ANALOGS USING MM3

Energy surfaces for the relative orientations of the pyranosyl rings of alpha,alpha-, alpha,beta-, and beta,beta-trehalose and analogues were generated with MM3. Sixteen starting conformations of the rotatable side groups of alpha,beta-trehalose were considered, while only 10 conformations were needed for alpha,alpha- and beta,beta-trehalose because of molecular symmetry. Energies were calculated at 20-degrees increments of the two torsional angles of the glycosidic linkage, but otherwise the molecules were fully relaxed. The structure at the overall minimum for alpha,alpha-trehalose agrees well with that found in crystal structures, and also agrees with interpretations of NMR and optical rotation data. The energy surfaces for the three trehaloses differ greatly from each other, but are each similar to those for the corresponding three 2-(6-methyltetrahydropyran-2-yloxy)6-methyltetrahydropyrans. This suggests that linkage type (axial or equatorial) is more important than exocyclic substituents in determining trehalose conformations. A comparison with surfaces from the corresponding 5a-carba trehalose analogues illustrates that the exo-anomeric effect is important in determining disaccharide conformation.