1-N-glycyl beta-oligosaccharide derivatives as stable intermediates for the formation of glycoconjugate probes.
Incubation of reducing sugars in ammonium bicarbonate was found to be a simple procedure for the formation of beta-D-glycosylamines of purified complex oligosaccharides in 70-80% yield. These provide valuable intermediates for the synthesis of a wide range of oligosaccharide probes and derivatives by acylation of the 1-amino function. The 1-amino function showed different rates of reactivity with different reagents. In general, interactions with large ring systems such as the fluorophores dansyl chloride and carboxyfluorescein gave 10-20% yields of products, which consisted of mixtures of both anomeric forms, whereas smaller acylating reagents gave near-quantitative yields of the desired beta-D-derivatives. Steric effects may explain differences in reactivity. N-Chloroacetamido derivatives could be obtained in high yield with retention of the beta-anomeric configuration. Subsequent ammonolysis of the chloroacetamido function afforded the corresponding N-glycyl beta-derivatives. The linker thereby introduced retains the amino function, possesses the useful properties of fixed anomeric configuration, improved stability, and uniform reactivity with a variety of reagents, and is structurally analogous to an asparagine side chain. The potential therefore exists for the generation of oligosaccharide derivatives tailored for different applications.
Manger
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Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, U.K.
Rademacher
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Dwek
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D000117:Acetylglucosamine / Q000737:chemistry; D000215:Acylation; D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D003619:Dansyl Compounds / Q000737:chemistry; D005452:Fluoresceins / Q000737:chemistry; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D013552:Swine
D003619:Dansyl Compounds; D005452:Fluoresceins; D006001:Glycoconjugates; D009844:Oligosaccharides; C024098:6-carboxyfluorescein; C029038:dansyl chloride; D000117:Acetylglucosamine