Optimizing glycosylation reaction selectivities by protecting group manipulation

Due to their biological importance, oligosaccharides and glycoconjugates have recently gained much attention. Investigations of such compounds often require chemically synthesized oligosaccharides. In the oligosaccharide synthesis, glycosylation reaction is frequently the most important step. Recently, one-pot multi-step glycosylations have become popular using the glycosyl donors with different reactivities and a polymer-supported technology that can reduce the laborious purification operations. For such methodologies, stereoselective glycosylation is essential. Compared to the 1,2-trans-glycoside formation, highly cis-selective glycosylation has remained relatively elusive. To enhance cis-selectivity, protection of the 2-position using a benzyl type ether and solvent effects are often employed. Recent reports have described the manipulation of protecting groups to afford novel donors that allow improved cis-selective glycosylation. This manuscript reviews such donors that have been reported within the last five years. We hope this manuscript proves to be helpful in furthering the chemical syntheses of oligosaccharides while improving our understanding of the glycosylation reaction including stereoelectronic effects.