Rationalizing the Stereoelectronic Influence of Interglycosidic Bond Conformations on the Reactivity of 1,4-O-Linked Disaccharide Donors

Disaccharide donors are key precursors in convergent glycan synthesis strategies. Unexpectedly, we observed that disaccharide thioglycosyl donors containing 1,4-O-linked α-glycosidic bonds are much more reactive than their β-analogues with the same protecting group pattern. Herein, we rationalized that such a difference in their reactivity is attributed to the conformation of the 1,4-O-interglycosidic bond which is controlled by anomeric and exo-anomeric effects. Moreover, the conformational preferences of these donors are dictated by the dihedral angles ϕ and ψ of their interglycosidic linkages and the torsional angle ω of their side chain along the C5-C6 bond. This fundamental research clarifies how the long-range stereoelectronic effects from the nonreducing end sugar can influence the reactivity of the leaving group at the reducing end and the behavior of disaccharide donors thereof.