Synthesis of daunorubicin conjugates with fragments of H type 5, Lea, Lex antigens and N-fucoglycan

Abstract

Daunorubicin was conjugated with spacered N-glycosides of di- and trisaccharides containing terminal α-l-fucopyranose residues. The synthesis was carried out by N-monoalkylation of daunorubicin hydrochloride (1) in aqueous DMF in the presence of NaHCO₃ using N-β-glycoside N-bromoacetylglycyl derivatives, namely, α-l-Fucp-(1→2)-β-d-Galp-(1→4)-β-d-Glcp-NHCOCH₂NHCOCH₂Br (2a), α-l-Fucp-(1→4)-[β-d-Galp-(1→3)]-β-d-GlcpNAc-NHCOCH₂NHCOCH₂Br (3a), α-l-Fucp-(1→3)-β-d-GlcpNAc-NHCOCH₂NHCOCH₂Br (4a), and α-l-Fucp-(1→6)-β-d-GlcpNAc-NHCOCH₂NHCOCH₂Br (5a). The conjugates of daunorubicin were obtained as hydrochlorides (2b-5b) in 40% yield. Their oligosaccharide components are fragments of H type 5, Le^a, Le^x antigens and N-fucolglycan, respectively. 0(I) Erythrocytes hemagglutination inhibition assay was performed with conjugates 2b–5b and Ulex europaeus (UEA 1), Lotus tetragonolobus (LTA), and Laburnum anagyroides (LAA) plant fucolectins.