Libraries of Oligosaccharides

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. 

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A list of recent papers (31, 32) and reviews (33-38) dealing with combinatorial libraries of oligosaccharides should give a flavor of the present and the future to the interested reader. 

Glycosylation of acceptor polyols has also been used for the concomitant introduction of multiple copies of the same residue,81,85 86 89 and for generating combinatorial libraries of oligosaccharides.199-202 In a number of cases, the regioselectivity could be... 

T. Mizuochi, R. W. Loveless, A. M. Lawson, W. Chai, P. J. Lachmann, R. A. Childs, S. Thiel, T. Feizi, A library of oligosaccharide probes (neoglycolipids) from N-glycosylated proteins reveals that conglutinin binds to certain complex type as well as high-mannose type oligosaccharide chains. 3. Biol Chem. 1989,264, 13834-13839. 

Applications Using these protocols, an oligosaccharide library was prepared (Table 11.2). The synthesis of a tetrasaccharide in general, takes 3-15 min, and with the aid of the computer program, a library of individual oligosaccharides can be assembled rapidly. 

The synthesis of libraries of structurally defined compounds can potentially be achieved either by split-mix synthesis or by parallel synthesis of individual compounds. The synthesis requires a reliable methodology of oligosaccharide synthesis, where stereochemistry and regioselectivity have to be achieved unlike other library approaches. Development of synthetic methodologies that can provide access to any oligosaccharide structure is underway. 

Takahashi et al.45 used a 4-hydroxybenzenesulfonate linker on Syn-Phase polystyrene Crowns to prepare glucose derivatives and macrocycles (Scheme 20). Displacement of the monosaccharide-supported Crowns 70 with nucleophiles such as azide, iodide, and acetate gave the respective 6-substituted glucose derivatives 71, 72, and 73 in excellent purities and yields. The authors suggest that this methodology could be utilized for the preparation of oligosaccharide libraries. 

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