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 B_1,4 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.