Oligosaccharides combinatorial chemistry

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. 

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... 

While PEG-based supports are widely used for liquid-phase combinatorial chemistry, other non-PEG-based soluble polymers have also been reported for combinatorial applications. A recent review (276) contains an exhaustive list of homo- and copolym-eric soluble supports used in peptide, oligonucleotide, and oligosaccharide synthesis, including combinatorial chemistry. Two of these supports have also been used for small organic molecule synthesis. Homopolymeric polyvinyl alcohol was used in conjunction with PEG for a protection/derivatization strategy in solution (284), and the copolymer between isopropylacrylamide and acrylic acid was used in the catalytic hydrogenation of a Cbz group (285). 

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... 

Other cla.sses of therapeutically important compounds that have been. synthesized successfully by u.sing solid-pha.se combinatorial chemistry include carbohydrates and natural products. Polysaccharides ate important for various carbohydrate-protein interactions. Carbohydrate antibiotics, including vancomycin and aminoglycosides, have been the targets of combinatorial chemistry, as well as complex oligosaccharides like the one shown in Figure 3-9." A vari-... 

As a consequence of the progress and success of diverse oligomer libraries, experts in combinatorial synthetic oligomers, glycopeptide and oligosaccharide libraries, RNA-and DNA-aptamers have each contributed their news in these fields, while novel experimental examples of the use of templates in combinatorial chemistry for the solid-phase synthesis of multiple core structure libraries provide some insight to praxis-relevant work. 

Combinatorial chemistry uses such methods to make mixtures of many possible compounds (called libraries) that can then be screened for the desired property to select those compounds that are active.149 The methods are suitable not only for polypeptides, but also for oligonucleotides,150 oligosaccharides,151 and a variety of small molecules, including many heterocyclic compounds. The method s popularity is because our knowledge of the inter-... 

Scheme 16. Directed combinatorial chemistry usingchemoenzymatically synthesized oligosaccharide building blocks.

Hilaire, P.M.St. and Meldal, M., Glycopeptide and oligosaccharide libraries, in Combinatorial Chemistry Synthesis, Analysis, Screening, Jung, G., Ed., WUey-VCH, Weinheim, 1999, chap. 8. 

Building block for oligosaccharide syntheses. Potential use in carbohydrate combinatorial chemistry. 

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