Conformational studies of methyl 3-O-methyl-alpha-D-arabinofuranoside: An approach for studying the conformation of furanose rings

A computational method for probing furanose conformation has been developed using a methylated monosaccharide derivative 1. First, a large library of conformers was generated by a systematic pseudo Monte Carlo search followed by optimization with the AMBER molecular mechanics force field. A subset o f these conformers was then subjected to ab initio and density functional t heory calculations in both the gas and aqueous phases. These calculations i ndicate that entropic contributions to the Gibbs free energy are important determinants of the Boltzmann distribution for the conformational preferenc es of 1 in the gas phase. The results obtained at each level of theory are discussed and compared with the experimentally determined conformer distrib ution from NMR studies in aqueous solution. In addition, the ability of eac h level of theory to reproduce the experimentally measured H-1-H-1 coupling constants in 1 is discussed. Empirical Karplus equations and density funct ional theory methods were used to determine average (3)J(H1,H2), (3)J(H2,H3 ), and (3) J(H3,H4) for each level of theory. On the basis of this comparis on, consideration of solvation with the MN-GSM model provided good agreemen t with the experimental data.