Synthesis of C-Glycosyl Amino Acid Building Blocks Suitable for the Solid-Phase Synthesis of Multivalent Glycopeptide Mimics

Five C-glycosyl functionalized lysine building blocks, featuring C-glycosidic derivatives of α-rhamnose, α-mannose, α-galactose, β-galactose, and β-N-acetyl glucosamine have been designed and synthesized. These derivatives, equipped with acid-labile protecting groups, are eminently suitable for solid-phase synthesis of multivalent glycopeptides. The lysine building blocks were prepared from C-allyl glycosides that underwent a Grubbs cross-metathesis with an acrylate, followed by a reduction of the C=C double bond in the resulting α,β-unsaturated esters, and liberation of the carboxylate to allow condensation with a lysine side chain. The thus obtained C-glycosides, five in total, were applied in the solid-phase peptide synthesis (SPPS) of three glycopeptides, showing the potential of the described building blocks in the assembly of well-defined mimics of homo- and heteromultivalent glycopeptides and glycoclusters.