The conformational preferences of the furanose rings in methyl R-D-arabinofuranoside (1), methyl β-D-arabinofuranoside (2), methyl R-D-lyxofuranoside (3), methyl β-D-lyxofuranoside (4), methyl R-Dribofuranoside (5), methyl β-D-ribofuranoside (6), methyl R-D-xylofuranoside (7), and methyl β-Dxylofuranoside (8) have been studied in the gas (B3LYP/6-31+G**//B3LYP/6-31G*) and aqueous (B3LYP/ 6-31+G**//SM5.42/BPW91/6-31G*) phases. The results of these theoretical investigations are compared to previous theoretical and experimental results to determine the northern and southern minima in solution for each glycoside.

The solution conformation of a furanose ring can be assessed through PSEUROT analysis of three-bond (1)H-(1)H coupling constants ((3)J(HH)) of the ring hydrogens. For each coupling constant, PSEUROT requires two parameters, A and B, which are used to translate the H[bond]C[bond]C[bond]H dihedral angle predicted from the (3)J(HH) into an endocyclic torsion angle from which the identity of the conformers can be determined. In this paper, we have used density functional theory methods to generate a family of envelope conformers for methyl furanosides 1-8. From these structures, A and B were calculated for each H[bond]C[bond]C[bond]H fragment. In turn, the values of these parameters for the arabinofuranose ring were used in PSEUROT calculations to determine the conformers populated by monosaccharides 1 and 2 as well as the furanose rings in oligosaccharides 9-15. The results of these analyses are consistent with the low-energy conformers identified from previous computational and X-ray crystallographic studies of 1 and 2.

The effects of electronegativity and stereochemistry upon three bond 1 H-1 H coupling constants ( 3 J H,H ) are widely appreciated and have been taken into consideration in the development of Karplus equations for H-C-C-H fragments. These equations have found particular use in the conformational analysis of molecules containing aldopentofuranose residues. This paper demonstrates the effect of anomeric stereochemistry upon 3 J C1,H4 in aldopentofuranosides and proposes Karplus equations that account for this effect. These new equations are shown to provide improved results for the determination of furanose ring conformation when compared to those obtained solely with 3 J H,H data. The equations described here should be applicable to furanose derivatives containing any substituent at the anomeric center.

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 of these conformers was then subjected to ab initio and density functional theory calculations in both the gas and aqueous phases. These calculations indicate that entropic contributions to the Gibbs free energy are important determinants of the Boltzmann distribution for the conformational preferences of 1 in the gas phase. The results obtained at each level of theory are discussed and compared with the experimentally determined conformer distribution from NMR studies in aqueous solution. In addition, the ability of each level of theory to reproduce the experimentally measured 1H-1H coupling constants in 1 is discussed. Empirical Karplus equations and density functional theory methods were used to determine average 3J(H1,H2), 3J(H2,H3), and 3J(H3,H4) for each level of theory. On the basis of this comparison, consideration of solvation with the MN-GSM model provided good agreement with the experimental data.