Convergent syntheses of the methyl glycosides of the branched pentasaccharide a-L-Rhap-(1-2)-[a-D-Glcp-(1-3)]-a-L-Rhap-(1-3)-a-L-Rhap-(1-3)-b-D-GlcNAcp [A(E)BCD], featuring the biological repeating unit of the O-specific polysaccharide of Shigella flexneri serotype 5a, and of a related linear tetrasaccharide (EBCD) are described. The strategy, based on the trichloroacetimidate methodology, relied on the use of a key EB disaccharide donor and appropriate CD acceptors. The use of an isopropylidene acetal to block OH-4 and OH-6 of residue D was found to be a suitable alternative to the employment of the more commonly used benzylidene acetal. Conformational analysis of EBCD-OMe and A(E)BCD-OMe was based on analysis of 1H and 13C chemical shifts and inter-proton distances data obtained by glycosylation pattern in A(E)BCD-OMe. Comparison of 1H and 13C chemical shifts of the two oligosaccharides with those of their corresponding sequences in the O-specific polysaccharide of S. flexneri 5a showed that the two oligosaccharides presented a distribution of solution conformations similar to that in the O-specific polysaccharide. The conformation of A(E)BCD-OMe was investigated by two approaches: (i) energy minimisation based on ROE-derived distances with the DISCOVER program and (ii) a conformational searching method (the CICADA algorithm interfaced with MM3 force-field). The minimised conformation obtained by the former approach was in total agreement with the average of the two major families of conformations resulting from the CICADA calculations.
Oligosaccharides, conformational analysis, glycosylation
Publication DOI: 10.1002/1099-0690(200208)Journal NLM ID: 9805750Publisher: Wiley-VCH
Institutions: Unite de Chimie Organique, URA CNRS 2128, Institut Pasteur, Unite de Resonance Magnetique Nucleaire des Biomolecules, URA CNRS 2185, Institut Pasteur, CERMAV-CNRS, affiliated to Universite Joseph Fourier, 38041 Grenoble BP53, Cedex 09, France
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