Oligosaccharide Synthesis and Library Assembly by One-Pot Sequential Glycosylation Strategy

Abstract

The oligosaccharide residue in glycoconjugates located in cell membranes is responsible for intercellular recognition and interaction: it acts as a receptor for proteins, hormones, and microorganisms and governs immune reactions. These significant activities have stimulated great interest in the field of oligosaccharides and glycoconjugates. Although many advances have been made in the synthesis of oligosaccharides, more convenient and efficient methods are still needed. This review describes one of these new methods-the one-pot sequential glycosylation approach as a potent tool for oligosaccharide assembly. The oligosaccharide library construction in a one-pot fashion is also summarized.

Toward Automated Oligosaccharide Synthesis

“…The programmable one‐pot approach also represents an efficient combinatorial method suitable for the construction of a saccharide library 26c. The method has been successfully applied to assemble designed linear and branched oligosaccharide structures, construct a 33‐membered oligosaccharide library,29, 42 and diversify the sugar domain of natural products, such as aminoglycosides and vancomycin derivatives bearing different sugar substituents 43…”

Immunotherapy for cancer: synthetic carbohydrate-based vaccines

“…Several research groups have demonstrated that chemo-selective, orthogonal and iterative glycosylation strategies, which exploit differential reactivities of anomeric leaving groups, allow several selected glycosyl donors to react in a specific order resulting in a single oligosaccharide product. [47][48][49][98][99][100] Methods for solid-phase oligosaccharide synthesis have been reported and these procedures shorten oligosaccharide synthesis by removing the need to purify intermediate derivatives. 51,101 A crucial step in the chemical synthesis of glycopeptide vaccine candidates is the merger of carbohydrate and peptide chemistry.…”

One-Pot Synthesis of Oligosaccharides by Combining Reductive Openings of Benzylidene Acetals and Glycosylations

“…Furthermore, many laboratories have demonstrated that chemoselective, orthogonal and iterative glycosylation strategies, which exploit differential reactivities of anomeric leaving groups, allow several selected glycosyl donors to react in a specific order resulting in a single oligosaccharide product. [12][13][14][15][16][17] To further streamline the process of oligosaccharide assembly, we report here a strategy whereby a regioselective opening of a benzylidene acetal and glycosylations are combined in a one-pot multi-step synthetic procedure. The attraction of the approach is that it makes it possible to assemble branched oligosaccharides by a one-pot procedure; a task that cannot readily be accomplished by chemoselective, orthogonal and iterative glycosylations.…”

“…To streamline the preparation of complex oligosaccharides, one-pot multistep approaches for selective monosaccharide protection and oligosaccharide assembly are being pursued, which do not require an intermediate workup and purification step and hence speed-up the process of chemical synthesis considerably. , For example, the observation that acetal formation, regioselective reductive opening of arylidene acetals, reductive etherification, and acetylation can be catalyzed by triflic acid (TfOH) or trimethylsilyl triflate (TMSOTf) made it possible to program these reactions in tandem by sequential addition of reagents to give easy access to a wide variety of selective protected monosaccharide building blocks. Furthermore, many laboratories have demonstrated that chemoselective, orthogonal and iterative glycosylation strategies, which exploit differential reactivities of anomeric leaving groups, allow several selected glycosyl donors to react in a specific order resulting in a single oligosaccharide product. – …”

“…Furthermore, many laboratories have demonstrated that chemoselective, orthogonal and iterative gly- cosylation strategies, which exploit differential reactivities of anomeric leaving groups, allow several selected glycosyl donors to react in a specific order resulting in a single oligosaccharide product. [12][13][14][15][16][17][18] Several reports have also shown that removal of silyl and trityl ethers can be combined with glycosylations. [19][20][21][22] To further streamline the process of oligosaccharide assembly, we report here a strategy whereby a regioselective opening of a benzylidene acetal and glycosylations are combined in a one-pot multistep synthetic procedure (Scheme 1).…”