215381-30-9Relevant academic research and scientific papers
Synthesis of a branched heptose- and kdo-containing common tetrasaccharide core structure of haemophilus influenzae lipopolysaccharides via a l,6-anhydro-l-glycero-β-d-manno-heptopyranose intermediate
Bernlind, Christian,Oscarson, Stefan
, p. 7780 - 7788 (2007/10/03)
The synthesis of a common tetrasaccharide core structure of Haemophilus influenzas lipopolysaccharides, β-D-glucopyranosyl-(1→4)-[L-glycero-α.-D-manno-heptopyranosyl- (1→3)]-L-glycero-α-Dmanno-heptopyranosyl-(1→5)-3-deoxy-α- D-manno-octulopyrahoside, and the trisaccharide β-D-glucopyranosyl(1→4)-[L-glycero-α-D-manno-heptopyranosyl- (1→3)]-L-glycero-α-D-manno-heptopyranoside is described. The oligosaccharides are synthesized as glycosides of a bifunctional spacer, 2-(4-aminophenyDethanol, to allow the subsequent formation of immunogenic glycoconjugates, which will be evaluated as well-defined glycoconjugate vaccine candidates. The syntheses of the 3,4branched structures were accomplished using a 1,6-anhydro-L-glycero-β-D-manno-heptopyranose intermediate to diminish the steric crowding between the 3- and 4-substituent. This intermediate was effectively synthesized from a mannose precursor via a stereoselective one-carbon elongation using a Barbier reaction (which was found to be more convenient than a Grignard reaction) and anhydro bridge formation through an internal glycosylation of a 6-O-trimethylsilylated ethyl thioheptoside using NIS/TfOH as a promoter. The 3- and 4-substituent were readily introduced into the 1,6-anhydro intermediate by glycosylation reactions using thioglycosides as donors and NIS/TfOH as a promoter, a task which has not been possible using acceptors with equatorial 3,4substituents. Acetolysis of the anhydro bridge followed by conversion into the ethyl thioglycoside afforded a trisaccharide donor, which, in NIS/TfOH-promoted couplings to the spacer and to a Kdo acceptor followed by deprotection, efficiently gave the two target compounds.
