Glycosylation on Unprotected or Partially Protected Acceptors

Abstract

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.

Site-Selective Modification of (Oligo)Saccharides

“…However, lessons learned from the partly protected monosaccharides, such as organocatalysts like in a recent contribution from Wendlandt and Jacobsen et al, 57 that allow discriminating between the secondary hydroxy groups in the acceptor can eventually be translated to the fully unprotected carbohydrates. 58 …”

“…For example, the method of Fairbanks can only be applied using GlcNAc donors and the method of Miller and Schepartz only works for sucrose acceptors. However, lessons learned from the partly protected monosaccharides, such as organocatalysts like in a recent contribution from Wendlandt and Jacobsen et al, that allow discriminating between the secondary hydroxy groups in the acceptor can eventually be translated to the fully unprotected carbohydrates …”

Boronic Acid-Catalyzed Regioselective Koenigs–Knorr-Type Glycosylation

“…The regioselective transformation of unprotected or partially protected glycosyl acceptors eliminates the need for the tedious manipulation of protection/deprotection sequences and provides a powerful strategy for synthesizing complex and diverse multifunctionalized carbohydrates . The method widely used to realize the construction of a new glycosidic linkage, which forms the basis of synthetic carbohydrate chemistry, is regioselective glycosylation triggered by the formation of a nucleophilic tin acetal using a stoichiometric amount of n Bu 2 SnO. − The development of regioselective glycosylation using less toxic organoboron compounds began in the early 2000s.…”

Chemical and chemoenzymatic synthesis of ganglioside(mimic)s and sulfoglycolipids

“…Another op� on to control regioselec� vity is by exploi� ng hydroxyl reac� vity. 100,101 As an example, in the synthesis of ganglio-series oligosaccharides, the lactose acceptor can have both 3-and 4-hydroxyls as possible sites for glycosyla� on. Due to the low reac� vity of the axial C-4 hydroxyl group, a (near) selec� ve glycosyla� on with C-3 can be obtained.…”