Synthesis of monomeric and dimeric repeating units of the zwitterionic type 1 capsular polysaccharide from Streptococcus pneumoniae.
Zwitterionic polysaccharides (ZPSs) from Bacteroides fragilis and Streptococcus pneumoniae display unique T-cell activities. The first synthesis of a hexasaccharide representing two repeating units of the zwitterionic capsular polysaccharide from S. pneumoniae type 1 (Sp1) is reported. Key elements of the approach are stereoselective construction of 1,4-cis-alpha-galactose linkages based on a reactive trichloroacetimidate donor that incorporates a 6-O-acetyl group, which may contribute to the high alpha selectivity in glycosylation. After assembly of the fully protected hexasaccharide from five monosaccharide synthons 2-4, 24 and 25, selective deprotection of the primary hydroxyl groups of the four galactose residues followed by oxidation to the corresponding uronic acids provides hexasaccharide 19. The trisaccharide counterpart 1 was synthesized in similar fashion from three synthons, 2-4. This approach employed both conventional and dehydrative glycosylation methodologies and avoids the use of poorly reactive uronic acid derived glycosyl donors and acceptors.
Wu
Xiangyang
X
Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Cui
Lina
L
Lipinski
Tomasz
T
Bundle
David R
DR
D016667:Bacterial Capsules / Q000737:chemistry*; D010084:Oxidation-Reduction; D011134:Polysaccharides / Q000138:chemical synthesis; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D013237:Stereoisomerism; D013296:Streptococcus pneumoniae / Q000737:chemistry*; D014574:Uronic Acids / Q000737:chemistry
D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D014574:Uronic Acids