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Convergent Synthesis, NMR and Conformational Analysis of Tetra‐ and Pentasaccharide Haptens of the Shigella flexneri Serotype 5a O ‐Specific Polysaccharide
Author(s) -
Mulard Laurence A.,
Clément MarieJeanne,
Imberty Anne,
Delepierre Muriel
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200208)2002:15<2486::aid-ejoc2486>3.0.co;2-e
Subject(s) - chemistry , shigella flexneri , residue (chemistry) , tetrasaccharide , stereochemistry , polysaccharide , glycosylation , chemical shift , disaccharide , nuclear magnetic resonance spectroscopy , carbohydrate conformation , acetal , organic chemistry , escherichia coli , biochemistry , gene
Convergent syntheses of the methyl glycosides of the branched pentasaccharide α‐ L ‐Rha p ‐(1⇄2)‐[α‐ D ‐Glc p (1⇄3)]‐α‐ L ‐Rha p ‐(1⇄3)‐α‐ L ‐Rha p ‐(1⇄3)‐β‐ D ‐GlcNAc p [ 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 1 H and 13 C chemical shifts and inter‐proton distances data obtained by NMR spectroscopy. The data showed that residue A had no influence on the conformational behaviour of residue E , although these two residues were involved in a 2,3‐ cis vicinal glycosylation pattern in A(E)BCD‐OMe . Comparison of 1 H and 13 C 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. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)