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.
Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Xiangyang
X
Wu
Lina
L
Cui
Tomasz
T
Lipinski
David R
DR
Bundle
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