Large oligosaccharide-based glycodendrimers

Abstract

Carbohydrate-based dendritic structures composed of 21 and 27 monosaccharide residues have been synthesized in a convergent manner from trisaccharide building blocks. The oligosaccharide AB2 monomers are based on a maltosylβ(1 → 6) galactose structure, which has been modified to include two methylamino groups at the primary positions of the glucosyl residues. Reductive alkylation of the secondary amino groups, with the innate formyl function of a second oligosaccharide monomer, allows for the chemoselective construction of dendritic wedges, while employing a minimal number of protecting groups. The first-generation dendron can be coupled either to another AB2 monomer, to give a second-generation dendron, or to a tris[2-(methylamino)ethyl] amine-based core moiety, to provide a carbohydrate-based dendrimer. Alternating α- and β-glucosyl residues in the monomers and dendrons, simplifies 1H NMR spectra as a consequence of spreading out the anomeric proton signals. Monomers and dendrons were characterized by extensive one- and two-dimensional NMR spectroscopy in addition to FAB, electrospray, and MALDI-TOF mass spectrometry. Molecular dynamics simulations revealed similar conformations in the dendrons as in the isolated trisaccharide repeating units.