Reactivity differences in glycosidic bond cleavage between phenyl β-d-glucoside and xyloside under basic conditions: mechanistic insights from kinetic and computational approaches

The β-glucopyranosyl and β-xylopyranosyl moieties are abundant in lignocellulose and share nearly identical chemical structures, differing mainly in the presence or absence of a hydroxy group at C₆. Despite this similarity, the degradation characteristics of these moieties under various conditions, such as acidic or alkaline environments, differ significantly. Our research group aims to quantitatively understand the reactivity differences between glucosyl and xylosyl moieties. This study focused on the glycosidic bond cleavage reactions of phenyl β-d-glucopyranoside (PhG) and its xylosyl counterpart (PhX) under alkaline conditions. Kinetic analysis of the degradation reactions of PhG and PhX in 1.0 mol/L NaOD/D₂O under nitrogen showed that these bond cleavages follow the S_NicB mechanism, involving nucleophilic attack by the C₂-oxyanion on C₁ in the ¹C₄-conformer. PhX degraded significantly faster than PhG, explained by PhX’s entropic advantage in activation entropy, ΔS^‡ [ΔS^‡ =  − 22.0 (PhG), − 10.8 (PhX) cal/mol K at 100 °C]. Theoretical calculations at the SCS-MP2//DFT(M06-2X) level revealed that in the nucleophilic substitution process of PhG’s ¹C₄-conformer, a strong hydrogen bond forms between the departing phenolate ion and the C₆ hydroxy group, causing entropic destabilization of the transition state. Additionally, the ¹C₄-conformer of PhG is less stable than that of PhX from both potential energetic and entropic perspectives, further contributing to their reactivity differences. These findings suggest that reactivity differences between PhG and PhX are explained by multiple factors, including conformational flexibility and ease of glycosidic bond cleavage.