Correlated C-C and C-O bond conformations in saccharide hydroxymethyl groups: Parameterization and application of redundant 1H-1H, 13C-1H and 13C-13C NMR J-couplings

Methyl α- and β-pyranosides of d-glucose and d-galactose 1−4 were prepared containing single sites of 13C-enrichment at C4, C5, and C6 (12 compounds), and 1H and 13C{1H} NMR spectra were obtained to determine a complete set of J-couplings (1J, 2J, and 3J) involving the labeled carbon and nearby protons and carbons within the exocyclic hydroxymethyl group (CH2OH) of each compound. In parallel theoretical studies, the dependencies of 1J, 2J, and 3J involving 1H and 13C on the C5−C6 (ω) and C6−O6 (θ) torsion angles in aldohexopyranoside model compounds were computed using density functional theory (DFT) and a special basis set designed to reliably recover the Fermi contact contribution to the coupling. Complete hypersurfaces for 1JC5,C6, 2JC5,H6R, 2JC5,H6S, 2JC6,H5, 2JC4,C6, 3JC4,H6R, 3JC4,H6S, and 3JC6,H4, as well as 2JH6R,H6S, 3JH5,H6R, and 3JH5,H6S, were obtained and used to parametrize new equations correlating these couplings to ω and/or θ. DFT-computed couplings were also tested for accuracy by measuring J-couplings in 13C-labeled 4,6-O-ethylidene derivatives of d-glucose and d-galactose in which values of ω and θ were constrained. Using a new computer program, Chymesa, designed to utilize multiple J-couplings sensitive to exocyclic CH2OH conformation, the ensemble of experimental couplings observed in 1−4 were analyzed to yield preferred rotamer populations about ω and θ. Importantly, due to the sensitivity of some couplings, most notably 2JH6R,H6S, 2JC5,H6R, and 2JC5,H6S, to both ω and θ, unique information on correlated conformation about both torsion angles was obtained. The latter treatment represents a means of evaluating correlated conformation in 1,6-linked oligosaccharides, since ψ and θ are redundant in these linkages. In the latter regard, multiple, redundant scalar couplings originating from both sides of the glycosidic linkage can be used collectively to evaluate conformational correlations between ψ/θ and C5−C6 bond rotamers.