Combinatorial oligosaccharides

Fig. 11. Combinatorial oligosaccharide library approach in solution with an orthogonal...

The use of microfluidic systems in oligosaccharide synthesis is in its infancy and far from being automated. More extensive use and development of such systems will open up new ways to access high-throughput and combinatorial oligosaccharide libraries. 

Polymer-supported strategies of oligosaccharide syntheses are ideally suited to preparations of combinatorial oligosaccharide libraries since purification of all products of a particular synthetic step is done at the same time and it would not be expected that individual library members would be lost during the purification process. Both one-phase and two-phase polymer supported strategies have been examined, and a review was published recently [80]. More recent articles that were not discussed in this review include syntheses of disaccharide [81] and trisaccharide [82] libraries leading to the discovery of novel antibacterial agents [83], and prepa-... 

P.H. Seeberger, Solid Support Oligosaccharide Synthesis and Combinatorial Carbohydrate Libraries, Wiley, New York, 2004. 

Solid Support Oligosaccharide Synthesis and Combinatorial Carbohydrate Libraries... 

High selectivity and substrate specificity of glycosyl transferases make them valuable catalysts for special linkages in polymer-supported synthesis. There is, however, still a rather limited set of enzymes available to date, and the need to synthesize a variety of natural and non-natural oligosaccharides prevails. Particularly with regard to combinatorial approaches, chemical solid-phase oligosaccharide synthesis promises to meet the demands most effectively. 

The Sulfoxide Glycosylation Method and its Application to Solid-Phase Oligosaccharide Synthesis and the Generation of Combinatorial Libraries... 

Combinatorial approaches to the synthesis of libraries of peptides, nucleotides, and many classes of small organic molecules are well documented.35 However, the field of oligosaccharide combinatorial chemistry is still in its infancy.36 The slow development is due to the inherent complexities in the synthesis of oligosaccharides. 

These results demonstrate that O-glycosyl trichloroacetimidate-based oligosaccharide synthesis on solid support may eventually become a valuable alternative to solution-phase synthesis because useful experience is available for the selection of the polymer support and choice of the linker system and the glycosyl donor. Further standardization of the building blocks and the protective group pattern will finally provide the yields and the anomeric control in order to successfully plan automated syntheses of oligosaccharides also in a combinatorial manner. 

Combinatorial chemistry has provided new ways for the pharmaceutical industry and for academic researchers to address specific problems in a time- and resource-efficient manner. Given the involvement of specific oligosaccharide structures in signal transduction processes, combinatorial carbohydrate libraries are... 

A linker originally designed for solid-phase synthesis of peptides is the backbone amide linker (11) (BAL), this anchoring approach has now been extended to the combinatorial synthesis of diverse amide [31], hydroxamate [32], oligosaccharide [33] and heterocyclic small molecule libraries [34-36]. 

Scheme 5.6 Poly-LacNAc-derived oligosaccharides synthesized by combinatorial biocatalysis [80].

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