Synthesis of hexa- to tridecasaccharides related to Shigella dysenteriae type 1 for incorporation in experimental vaccines.
Hexa- to tridecasaccharides corresponding to the O-specific polysaccharide (O-SP) of the Gram-negative bacterium Shigella dysenteriae type 1 were synthesized in solution phase. The syntheses utilized tetra-, octa-, and dodecasaccharide intermediates that represent one to three contiguous tetrasaccharide repeating units of the O-SP [Synlett2003, 743]. These compounds were glycosylated with mono-, di-, and trisaccharide trichloroacetamidates, which were synthesized in this study. The excellent stereodirecting effect of 4,6-O-benzophenone ketals in glycosylation reactions of 2-azido-2-deoxy-glucopyranosyl donors was demonstrated. The free oligosaccharides were characterized by 1H and 13C NMR spectroscopy and by high-resolution mass spectrometry. The oligosaccharides described herein contain the 5-(methoxycarbonyl)pentyl aglycon for eventual attachment to immunogenic carriers using a recently published protocol [J. Org. Chem.2005, 70, 6987].
Pozsgay
Vince
V
Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, 31 Center Dr. Rm. 2A29, MSC 2423, Bethesda, MD 20892-2423, USA. pozsgayv@mail.nih.gov
Ekborg
Göran
G
Sampathkumar
Srinivasa-Gopalan
SG
D002240:Carbohydrate Sequence; D008969:Molecular Sequence Data; D019081:O Antigens / Q000737:chemistry; D009844:Oligosaccharides / Q000138:chemical synthesis*; D011134:Polysaccharides / Q000138:chemical synthesis*; D022281:Shigella Vaccines / Q000138:chemical synthesis*; D012762:Shigella dysenteriae / Q000737:chemistry* / Q000276:immunology
D019081:O Antigens; D009844:Oligosaccharides; D011134:Polysaccharides; D022281:Shigella Vaccines