Synthesis of an Aminooxy Derivative of the GM3 Antigen and Its Application in Oxime Ligation.

The anomeric aminooxy GM3 trisaccharide cancer antigen (Neu5Acα2,3Galβ1,4Glcβ-ONH2) has been chemically synthesized using a linear glycosylation approach. The key step involves a highly α(2,3)-stereoselective sialylation to a galactose acceptor. The Neu5Acα2,3Gal intermediate was functionalized as a donor for a [2 + 1] glycosylation, including a glucose acceptor that featured an O-succinimidyl group on the reducing end as an aminooxy precursor. The fully deprotected anomeric aminooxy GM3 trisaccharide was then conjugated to the immunologically relevant zwitterionic polysaccharide PS A1 via an oxime link.