Synthesis and Conformational Analysis of 6-C-Methyl-Substituted 2-Acetamido-2-deoxy-β-d-glucopyranosyl Mono- and Disaccharides

摘要

Several 6-C-substituted 2-acetamido-2-deoxy-β-d-glucopyranosides (β-d-GlcNAc monosaccharides >1a–>3a and 1,4-linked disaccharides >1b–>3b) were studied by solution NMR spectroscopy. Conformational analysis of the (6S)- and (6R)–C-methyl-substituted β-d-GlcNAc monosaccharides indicates that the stereodefined methyl groups impose predictable conformational biases on the exocyclic C-5–C-6 bond, as determined by ¹H-¹H and ¹³C–¹H coupling constants. Variable-temperature NMR experiments in methanol-d4 were performed to determine ΔΔH and ΔΔS values derived from the two lowest energy conformers. These indicate that while the influence of 6-C-methyl substitution on conformational enthalpy is in accord with the classic principles of steric interactions, conformational preference in solution can also be strongly affected by other factors such as solvent-solute interactions and solvent reorganization.