Oligosaccharide solid support synthesis

The Glycal Assembly Method on Solid Supports Synthesis of Oligosaccharides and Glycoconjugates... 

The development of the synthesis of peptides on solid supports has also had a strong impact on other areas of organic synthesis. From the very beginning, some research groups tried, with some success, to export the idea from peptide synthesis to, for instance, the monoalkylation and monoacylation of carboxylic acids,the synthesis of aldehydes and ketones, or to the use of resin-bound dienes or dienophiles to trap reactive intermediates.PI This pioneering work has been fundamental to the much more recent explosion of combinatorial chemistry on solid supports. Synthesis on solid supports has also found application in the synthesis of oligonucleotides, PI oligosaccharides,PI peptide-DNA hybrids,P°l and peptide nucleic acids (PNAs).P l... 

Since the level of complexity associated with the synthesis of oligosaccharides on a polymer support is much greater than that associated with the other two classes of repeating biooligomers, this task seemed for a long time too difficult to tackle. The development of protocols for the solid support synthesis of oligosaccharides and glycopeptides requires the scientists in the field to find solutions to several problems ... 

Three major strategies have been explored for the solid support synthesis of oligosaccharides and glycoconjugates. In one variation, the first carbohydrate is anchored to the support via its reducing end (see Scheme 1, Case 1). The carbohydrate bound to the solid support functions as an acceptor in the coupling event to a solution-based donor (D). In the cycle, a unique acceptor hydroxyl must be exposed... 

The field of solid phase synthesis has also benefited from enzyme technology. Several reports have described the use of sialyltransferases in the solid-supported synthesis of oligosaccharides that bear sialic acid [49]. Additionally, metabolic pathways have been harnessed by Bertozzi and coworkers to synthesize glycoconjugates on cell surfaces that bear modihed sialic acids [50]. 

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

Solid Support Oligosaccharide Synthesis and Combinatorial Carbohydrate Libraries... 

Scheme 1.2 Solid-phase oligosaccharide synthesis employing thioglycosidic linkages to different solid supports.

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. 

As was alluded to above, two possible approaches immediately present themselves for the synthesis of oligosaccharides on solid support. These involve the decision as to the mode of attachment of the first carbohydrate to the matrix. 

Scheme 2.2 General strategy for the synthesis of oligosaccharides on a solid support using the glycal assembly method.

Glycal assembly on a solid support eliminates the repetitive purifications usually associated with oligosaccharide synthesis. As a method, it has a certain generality as it does not require any specific enzymes or complex starting materials. Both natural and nonnatural sugars may be used in the constructions. 

A number of challenges still remain before a flexible, high-yielding, and absolutely selective strategy for the synthesis of oligosaccharides on the solid support becomes available. Once these problems are solved, the construction of an automated oligosaccharide synthesizer will become feasible. 

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