A Modular Chemoenzymatic Synthesis Of Disialosyl Globopentaosylceramide (Dsgb5cer) Glycan

The total synthesis of the oligosaccharide moiety of disialosyl globopentaosylceramide (DSGb5 Cer), a dominant ganglioside isolated from malignant renal cell carcinoma tissues, is reported. The synthetic strategy relies on a chemical alpha(2,6)-sialylation at the internal GalNAc unit of a Gb5 pentasaccharide backbone that furnishes a Neu5Ac alpha(2,6)GalNAc-linked hexasaccharide, suitable for an enzymatic alpha(2,3)-sialylation of the terminal Gal residue to construct a heptasaccharide glycan. Convergent access to this key alpha(2,6)-sialylated hexasaccharide was also achieved through a [3+3] glycosylation building upon a Gal beta-(1,3)[Neu5Ac alpha(2,6)]GalNAc-based trisaccharide donor and a Gb3 acceptor. The synthetic DSGb5 glycan bearing a 6-azidohexyl aglycon at the reducing end could undergo further regioselective functionalization. This approach represents a viable chemoenzymatic method for accessing complex ganglioside glycans and should be useful for the synthesis and biological investigation of DSGb5 derivatives.