Glycosylation on Unprotected or Partially Protected Acceptors

Over the last 30 years, there have been several methods developed for the synthesis of oligosaccharides, such as combinatorial synthesis, programmable one‐pot glycosylations, pre‐activation‐based chemo‐selective glycosylation strategy, random glycosylation, chemo‐enzymatic processes, and automated platforms. Distinguishing hydroxyl groups in carbohydrate monomers form the crux of oligosaccharides synthesis. The protection of hydroxyl groups stops glycosylation at undesired positions on carbohydrates, but additional steps are required to install and remove the protecting groups. The targeted functionalization of carbohydrates relies mostly on the protection of hydroxyl groups that are not supposed to undergo glycosylation and to leave the hydroxyl group unprotected where the glycosylation should occur. Numerous procedures to avoid or decrease protecting group manipulations have been developed for the synthesis of a single or an oligosaccharide library, such as glycosylation on unprotected or partially protected acceptors, and random glycosylation on unprotected acceptors. In this review, overall approaches for glycosylation on unprotected or partially protected acceptors in the synthesis of oligosaccharides and oligosaccharide libraries are summarized, the glycosylation on unprotected or partially protected carbohydrate acceptors with or without tin or boron mediation, and random glycosylation on unprotected or partially protected acceptors in solution phase or on solid phase are discussed.