Computational studies of the arabinofuranose ring: Conformational preferences of fully relaxed methyl alpha-D-arabinofuranoside

Two approaches for identifying the minimum energy conformers of methyl alph a -D-arabinofuranoside 1, in the gas phase have been explored and compared. In the first approach (the constrained envelope method), 30 previously rep orted envelope geometries of 1 were allowed to fully optimize at the B3LYP/ 6-31G* level, B3LYP/6-31+G** single-point energies of these optimized struc tures were also determined, which led to the identification of the T-3(4) a nd T-2(1) ring conformers as the Northern (N) and Southern (S) minima, resp ectively, with the latter being the global minimum. The importance of intra molecular hydrogen bonding was probed by optimizing another set of 30 envel ope geometries with initial geometries biased against the formation of thes e stabilizing interactions. These calculations led to the same two families of low-energy ring conformers (3T4 and 2T1); however, the N, and not the S , conformer was the global minimum without hydrogen bonding. The second app roach involved the identification of conformers for 1 through the use of a Monte Carlo search coupled with molecular mechanics and then further optimi zation of these structures at higher levels of theory (HF/6-31G* and B3LYP/ 6-31G*). Subsequent B3LYP/6-31+G** single-point energy calculations afforde d results that are similar to the constrained envelope method, but the stoc hastic approach led to more low-energy conformers, and to a new global mini mum. A comparison of these computational results with the experimentally de termined solution conformation of 1 is-also presented.