Stereoselective Synthesis of a C-Glycosidic Analog of N-Glucoasparagine

摘要

In diug design glycopeptides are of interest for the modification of biologically active peptides. Recent investigations revealed that the attachment of carbohydrates to peptides improves bioavailability, increases resistance to proteases, improves water solubility or enables them to penetrate the blood-brain barrier. Most synthetic glycopeptides contain the natural O- or N-glycosidic linkage between the sugar residue and the peptide backbone. To improve the metabolic stability, C-glycosidic amino acids are of interest because the carbon-carbon linkage at the anomeric center should increase the stability towards enzymes, acid, or base, Herein we present the synthesis of a C-glycosidic amino acid whose structure is analogous to that of N~4-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-L-as-paiagine (Asn(beta-GlcNAc) 1) Already existing analogs are the glycopeptoid 2, the retroamide 3, which was recently described by our group, and the C-glycosidic analog 4.