ABSTRACT
Syntheses of p-trifluoroacetamidophenyl glycosides of the haptenic pentasaccharide and the non-reducing disaccharide unit of the title pentasaccharide are reported. The synthesis of the terminal N-formylkansosamine unit started from methyl 6-deoxy-2,3-O-isopropylidene-alpha-L-lyxo- hexopyran-4-uloside which, after C-3 methylation, was transformed into a glycosyl donor [3-O-benzyl-4-N-benzylformamido-4,6-dideoxy-3-C-methyl-2-O-methyl- alpha,beta-L-mannopyranosyl trichloroacetimidate (20), and used for the synthesis of p-trifluoroacetamidophenyl (4-formamido-4,6-dideoxy-3-C-methyl-2-O-methyl-alpha-L-mannopyranosyl)- (1-->3)-6-deoxy-2-O-methyl-alpha-D-mannopyranoside (29). Ethyl (3-O-benzyl-4-N-benzylformamido-4,6-dideoxy-3-C-methyl-2-O-methyl- alpha-L-mannopyranosyl)-(1-->3)-4-O-benzyl-6-deoxy-2-O-methyl-1-thio- alpha-D-mannopyranoside (31), prepared by glycosylation of ethyl 4-O-benzyl-6-deoxy-2-O-methyl-1-thio-alpha-D-mannopyranoside with 20, served as glycosyl donor in a 2 + 3 block synthesis of the title pentasaccharide.
Subject(s)
Antigens, Bacterial/chemistry , Mycobacterium avium Complex/chemistry , Oligosaccharides/chemical synthesis , Carbohydrate Sequence , Glycopeptides/chemistry , Glycopeptides/immunology , Haptens , Molecular Sequence Data , Mycobacterium avium Complex/immunology , Oligosaccharides/immunology , Proteolipids/chemistry , Proteolipids/immunologyABSTRACT
MALDI-TOF mass spectroscopy was used for the molecular weight determination of protected synthetic oligosaccharides related to a cell surface bacterial polysaccharide. By-products containing chlorinated protecting groups caused isotopic patterns characteristic of the natural isotopic distribution of chlorine, were identified on the basis of isotopic distribution. 2,4,6-Trihydroxyacetophenone (THAP) as a matrix was better than 2,5-dihydroxybenzoic acid (DHB) for compounds containing chlorine, since monoisotopic resolution and no fragmentation were observed. In the post source decay (PSD) mode the identification of the oligosaccharide sequence through cleavage of the interglycosidic linkages was also possible, thus providing a sensitive and accurate tool for the structural verification of synthetic oligosaccharide intermediates.
Subject(s)
Oligosaccharides/chemistry , Shigella sonnei/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Carbohydrate Conformation , Carbohydrate Sequence , Molecular Sequence Data , Oligosaccharides/chemical synthesisABSTRACT
The functionalized, pyruvic acetal-containing haptenic trisaccharide, p-trifluoroacetamidophenyl 6-deoxy-2-O-(3-O-[4,6-O-(S)-(1-methoxycarbonylethylidene)-3-O-meth yl- beta-D-glucopyranosyl]-alpha-L-rhamnopyranosyl)-alpha-L-talopyranosid e (19), a component of the glycolipid from Mycobacterium avium serovar 8 was synthesized. For the preparation of the terminal pyruvic acetal-containing unit, benzyl 2-O-benzyl-3-O-methyl-beta-D-glucopyranoside (6) was condensed with methyl 2,2-di(ethylthio)propionate (1) in the presence of SO2Cl2-CF3SO3H catalyst to yield benzyl 2-O-benzyl-4,6-O-(S)-(1-methoxycarbonylethylidene)-3-O-methyl-beta -D- glucopyranoside (7S), which was then converted into the suitably substituted glycosyl donor 2-O-acetyl-4,6-O-(S)-(1-methoxycarbonylethylidene)-3-O-methyl-alph a-D- glucopyranosyl trichloroacetimidate (11). The disaccharide glycosyl acceptor p-nitrophenyl endo-3,4-O-benzylidene-6-deoxy-2-O-(2,4-di-O-benzyl-alpha-L-rhamnopyrano syl)- alpha-L-talopyranoside (15) was glycosylated with 11 in the presence of trimethyl trifluoromethanesulfonate to furnish the protected trisaccharide p-nitrophenyl 2-O-(3-O-[2-O-acetyl-4,6-O-(S)-(1-methoxycarbonylethylidene)-3-O-m ethyl-beta- D-glucopyranosyl]-2,4-di-O-benzyl-alpha-L-rhamnopyranosyl)-endo-3,4- O-benzylidene-6-deoxy-alpha-L-talopyranoside (16). After deprotection, this gave the spacer-armed unprotected haptenic trisaccharide 19.
Subject(s)
Glycoconjugates/chemistry , Mycobacterium avium/chemistry , Trisaccharides/chemical synthesis , Carbohydrate Conformation , Carbohydrate Sequence , Indicators and Reagents , Molecular Sequence Data , Molecular Structure , Mycobacterium avium/classification , Optical Rotation , Serotyping , Trisaccharides/chemistryABSTRACT
The chemical synthesis of the zwitterionic disaccharide 2 is described that corresponds to the repeating unit of the O-specific polysaccharide (1) of the gram-negative human pathogen Shigella sonnei. Passive hemolysis inhibition tests using a hyperimmune rabbit serum raised against S. sonnei showed that the serologic activity of the disaccharide 2 is nearly 2- to 3-fold higher than those of its component monosaccharides. NMR data of 2 are in support of the proposed structure of the O-specific polysaccharide.