- Oligosaccharides Corresponding to Biological Repeating Units of Shigella flexneri Variant Y Polysaccharide. 2. Synthesis and Two-Dimensional NMR Analysis of a Hexasaccharide Hapten
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The block synthesis of a hexasaccharide portion of the biological repeating unit, 2)-α-L-Rhap-(1->3)-α-L-Rhap-(1->3)-β-D-GlcpNAc-(1->, of the Shigella flexneri variant Y polysaccharide is described.The synthetic strategy relies on the use of the key trisaccharide intermediate, α-L-Rhap-(1->2)-α-L-Rhap-(1->3)-α-L-Rhap, as a glycosyl donor.Thus, the trisaccharide bromide in conjunction with the β-D-GlcpNPhth-(1->2)-α-L-Rhap-(1->2)-α-L-Rhap unit under Helferich conditions yielded the blocked hexasaccharide in 85percent yield.Attempts at coupling thetetrasaccharide donor, α-L-Rhap-(1->2)-α-L-Rhap-(1->3)-α-L-Rhap-(1->3)-β-D-GlcpNPhth, with the disaccharide acceptor, α-L-Rhap-(1->2)-α-L-Rhap, to give the hexasaccharide under a variety of conditions were unsuccessful.The blocked derivatives were synthesized as their allyl glycosides.Removal of the blocking groups, hydrogenation of the allyl group, and N-acetylation yielded the hexasaccharide hapten, α-L-Rhap-(1->2)-α-L-Rhap-(1->3)-α-L-Rhap-(1->3)-β-D-GlcpNAc-(1->2)-α-L-Rhap-(1->2)-α-L-Rhap, as its propyl glycoside, for use in inhibition studies with complementary monoclonal antibodies, and in NMR and X-ray studies.The detailed NMR analysis of the protected and deprotected hexasaccharides by use of two-dimensional NMR techniques is also described.
- Pinto, B. Mario,Reimer, Kerry B.,Morissette, David G.,Bundle, David R.
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p. 2650 - 2656
(2007/10/02)
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- Synthesis of Oligosaccharides Corresponding to Biological Repeating Units of Shigella flexneri Variant Y Polysaccharide. Part 1. Overall Strategy, Synthesis of a Key Trisaccharide Intermediate, and Synthesis of a Pentasaccharide
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The overall strategy for the synthesis of penta- up to octa-saccharides, representing the biological repeating unit of the Shigella flexneri serogroup Y lipopolysaccharide, is described.The key intermediate, the common terminal trisaccharide, α-L-Rhap-(1->2)-α-L-Rhap(1->3)-α-L-Rhap, has been synthesised by a series of Koenigs-Knorr reactions.A selectively protected rhamnose intermediate has been developed for the synthesis of this trisaccharide as its allyl glycoside.Allyl α-L-rhamnopyranoside was converted into the corresponding 2-O-benzoyl-4-O-benzyl derivative via a 2,3-orthobenzoate.Koenigs-Knorr reaction between this partially blocked rhamnoside and 2-O-acetyl-3,4-di-O-benzyl-α-L-rhamnopyranosyl chloride afforded the blocked disaccharide.Selective transesterification of the 2'-O-acetyl group in the presence of the 2-O-benzoate yielded the disaccharide, selectively deblocked at the C-2' position.Reaction with the same rhamnopyranosyl chloride gave the fully blocked trisaccharide.Deallylation, followed by treatment with NN-dimethyl(chloromethylene)ammonium chloride, then gave the corresponding trisaccharide chloride.In conjunction with the disaccharide methyl 2-O-(2'-acetamido-4',6'-O-benzylidene-2'-deoxy-β-D-glucopyranosyl)-3,4-di-O-benzyl-α-L-rhamnopyranoside, the synthesis of the blocked pentasaccharide was accomplished.Transesterification, followed by hydrogenolysis in aqueous acetic acid, afforded the pure pentasaccharide hapten, α-L-Rhap-(1->2)-α-L-Rhap-(1->3)-α-L-Rhap-(1->3)-β-D-GlcpNAc-(1->2)-α-L-Rhap, as its methyl glycoside, for use in binding studies and n.m.r. studies.
- Pinto, B. Mario,Morisette, David G.
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