Synthesis of a disialylated hexasaccharide of Type VIII Group B Streptococcus capsular polysaccharide

As part of our program to design, develop and prepare protective vaccines against the bacterial pathogens Group B Streptococcus, we report the synthesis of a disialylated hexasaccharide. This hexasaccharide represents a portion of the serotype-specific capsular polysaccharide of Type VIII that has the tetrasaccharide repeat unit {β-l-Rhap-(1→4)-β-d-Glcp-(1→4)-[α-Neu5Ac-(2→3)]-β-d-Galp-(1→4)}n. A tetrasaccharide corresponding to this repeat unit has been synthesized by us [E. Eichler, H.J. Jennings, D.M. Whitfield, J. Carbohydr. Chem., 16 (1997) 385–411]. Since the protective epitopes are believed to involve several repeat units, methods to extend this tetrasaccharide were examined. This objective requires a glycosylation of the unreactive OH-4 of the β-l-Rhap, which was accomplished by coupling a d-Galp glycosyl trichloroacetimidate donor with a β-l-Rhap-(1→4)-d-Glcp acceptor. Subsequent coupling of this trisaccharide as a donor to an α-Neu5Ac-(2→3)-d-Galp disaccharide acceptor gave a pentasaccharide. The pentasaccharide was deprotected and enzymatically sialylated using an α-(2→3)-sialyltransferase from Campylobacter jejuni to give the title hexasaccahride α-Neu5Ac-(2→3)-β-d-Galp-(1→4)-β-l-Rhap-(1→4)-β-d-Glcp-(1→4)-[α-Neu5Ac-(2→3)]-β-d-Galp-(1→O)-(CH2)3N3.