Synthesis of GD3-lactam: a potential ligand for the development of an anti-melanoma vaccine Original Research Article

The novel sialyl donor methyl (ethyl 4,7,8,9-tetra-O-acetyl-5-N,N-diacetylamino-3,5-dideoxy-2-thio-3-thiophenyl-d-erythro-β-l-gluco-non-2-ulopyranosid)onate was used for glycosylation of a lactosyl acceptor to give the GM3-trisaccharide derivative in 83% yield. Introduction of an azido group at C-9′′ of the GM3-trisaccharide derivative, transformation into a glycosyl acceptor, and sialylation with the above mentioned novel sialyl donor gave a GD3-trisaccharide in 50% yield. Reduction of the azido group gave the corresponding amine, which underwent spontaneous lactamization to the GD3-[1′′′–9′′]-lactam in an overall yield of 86%. Removal of protecting groups of over five steps, followed by per-O-acetylation gave an acetylated GD3-[1′′′–9′′]-lactam TMSEt glycoside in 27% overall yield. The acetylated GD3-[1′′′–9′′]-lactam TMSEt glycoside is suitable for glycosylation of linker-arms and the resulting linker-glycosides are planned to be coupled to carrier proteins, thus providing immunogens for trial vaccinations against malignant melanoma.