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RESEARCH PRODUCT

Carbohydrates as Polyfunctional Scaffolds in Combinatorial Synthesis

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Carbohydrates are inexpensive, polyfunctional molecules which contain a high density of stereogenic centers. Taking advantage of these particular properties monosaccharides like glucose or mannose have been used for the construction of peptidomimetics which simulate recognition sites of somatostatin or RGD ligands of integrins. Due to their poly functionality, carbohydrates are considered promising scaffolds for combinatorial syntheses either in solution or on solid phase. The application of carbohydrate scaffolds, however, requires sets of orthogonally stable, selectively removable protecting groups, and the challenge in this combinatorial strategy increases with increasing number of hydroxy groups involved in the combinatorial variation. A set of four orthogonally stable protecting groups in combination with a thioglycoside linker enabled the combinatorial diversification of galactose and glucose scaffolds in solid phase at all five positions. The use of amino uronic acids or diamino sugars makes functional group differentiation easier at carbohydrate scaffolds. In combinatorial syntheses on a resin-linked 2,6-diamino glucose scaffold, selective deprotection and functionalization at all four non-anomeric positions was achieved independent of the sequence. The concept of combinatorial synthesis has been extended to oligosaccharides and has been used, for example, for the construction of diversified moenomycin A structures.