Oligosaccharides solid-phase synthesis, combinatorial approach

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]. 

The advantage of solution phase approaches for constructing combinatorial libraries is the direct translation of known solution chemistry to library synthesis, versus the need to reengineer these chemistries to be compatible with the solid phase environment. Three approaches have been reported for generating solution phase oligosaccharide libraries [27-30]. The first reported strategy attempted to address one of the inherent challenges and costs associated with... 

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. 

In recent years, several groups have reported novel combinatorial approaches to the synthesis of oligosaccharides and carbohydrate mimics. In most cases, the development of efficient solid-phase reactions has been cmcial to the hbrary synthesis, as is discussed in this chapter. 

A number of groups became interested in this class of compounds, and the saccharide-peptide hybrids were coined carbopeptoids [10], glycotides [11], peptidosaccharides [12], or saccharopeptides [13]. In comparison to the formation of oligosaccharides, the complexity in the synthesis of saccharide-peptide hybrids is reduced since no a/ -anomers can be formed. In addition, the oligomerization can be carried out without protecting the hydroxy groups [14] since the amino function is more nucleophilic. We have demonstrated that the oligomerization can also be carried out on a solid phase [14], which opened the way to combinatorial approaches [15,16,17]. 

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