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 {beta-L-Rhap-(1 --> 4)-beta-D-Glcp-(1 --> 4)-[alpha-Neu5Ac-(2 --> 3)]-beta-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. Chern., 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 beta-L-Rhap, which was accomplished by coupling a D-Galp glycosyl trichloroacetimidate donor with a beta-L-Rhap-(1 --> 4)-D-Glcp acceptor. Subsequent coupling of this trisaccharide as a donor to an a-Neu5Ac-(:2 --> 3)-D-Galp disaccharide acceptor gave a pentasaccharide. The pentasaccharide was deprotected and enzymatically sialylated using an alpha-(2 --> 3)-sialyltransferase from Campylobacter jejuni to give the title hexasaccahride alpha-Neu5Ac-(2 --> 3)-beta-D-Galp-(1 --> 4)-beta-L-Rhap-(l --> 4)-beta-D-Glcp(1 --> 4)-[alpha-Neu5Ac-(2 --> 3)]-beta-D-Galp-(1 --> O)-(CH2)(3)N-3. (C) 1999 Elsevier Science Ltd. All rights reserved.