Conformational Effects on Glycoside Reactivity: Study of the High Reactive Conformer of Glucose

The effect of conformation on glycoside reactivity was investigated by studying the hydrolysis of
a selection of 3,6-anhydroglucosides as models for glucose in the highly reactive 1C4 conformation. Methyl
3,6-anhydro-β-d-glucopyranoside was found to hydrolyze 200−400 times faster than methyl glucosides in
the 4C1 conformation, while methyl 3,6-anhydro-β-d-galactopyranoside, which is in the B1,4 conformation,
was less reactive than methyl β-d-galactopyranoside. Methyl (3,6-anhydro-β-d-glucopyranosyl)-(1 → 6)-α-d-glucopyranoside, methyl (3,6-anhydro-α-d-glucopyranosyl)-(1 → 6)-α-d-glucopyranosyl-(1 → 6)-α-d-glucopyranoside, and methyl (3,6-anhydro-β-d-glucopyranosyl)-(1 → 6)-α-d-glucopyranosyl-(1 → 6)-α-d-glucopyranoside were prepared and found to react selectively at the anhydro residue. The finding that 1C4
conformers of glucosides are highly reactive species is in accordance with and supports previous results
showing that axial OH groups are less electron withdrawing than equatorial OH groups.