Conformational patterns of acetyl-protected aryl O-glucosides in solution and comparison with their S-glucoside...

We conducted the NMR conformational analysis of acetyl-protected aryl O- and S-β-glucosides carrying aryl substituents with varied electron-donating and electron-withdrawing character and studied the effects exerted by the aglycone, media polarity, and exocyclic anomeric chalcogen over the conformational equilibria of the glycosidic bond and hydroxymethyl group. The glycosidic bond flexibility proved remarkably sensitive to the nature of the chalcogen atom, with O-glucosides exhibiting rigid glycosidic bonds, which remained virtually fixed in the exo-syn conformer. In contrast, S-glucosides exhibit more flexible glycosidic bonds with exo-syn, exo-anti, and non-exo contributions. Interestingly, the glycosidic bond conformation in the S-glucosides proved more sensitive to the electronic properties of the aryl aglycone, where substitution with strong electron-withdrawing groups compromise the flexibility leading to stiffer glycosidic bonds with larger exo-syn occurrence. The electronic properties of the aryl aglycone also modulate the hydroxymethyl group conformations in both O- and S-glucosides. The substitution with strong electron-withdrawing groups promotes gt contributions at the expense of the predominating gg rotamer, being this effect solvent-sensitive and prominent in apolar media. Both chalcoglucoside series exhibited similar conformational patterns about the hydroxymethyl group.