Synthesis of a Tri- and Tetrasaccharide Fragment Specific for theShigella flexneriSerotype 5aO-Antigen. A Reinvestigation
作者:
Laurence A. Mulard,
Joël Ughetto-Monfrin,
期刊:
Journal of Carbohydrate Chemistry
(Taylor Available online 1999)
卷期:
Volume 18,
issue 7
页码: 721-753
ISSN:0732-8303
年代: 1999
DOI:10.1080/07328309908544033
出版商: Taylor & Francis Group
数据来源: Taylor
摘要:
Stereocontrolled, stepwise synthesis of methyl α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranoside (A(E)B, 1) and methyl 2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→2)-[α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranoside (DA(E)B, 2) is described; these constitute the methyl glycosides of fragments of theO-specific polysaccharide ofShigella flexneriserotype 5a. Two routes to trisaccharide1were considered. Route 1 involved the coupling of a precursor to residueAand a disaccharideEB, whereas route 2 was based on the condensation of a precursor to residueEand a disaccharideAB. Rather surprisingly, the latter afforded the β-anomer of1, namely methyl α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranoside as the major product. Route 1 was preferred. Overall, several observations made during this study suggested that, for the construction of higher fragments, a suitable precursor to rhamnoseAwould require protecting groups of low bulkiness at position 3 and 4. Therefore, the 2-O-acetyl-3,4-di-O-allyl-α-L-rhamnopyranosyl trichloroacetimidate (35) was the precursor of choice to residueAin the synthesis of the tetrasaccharide2. The condensation product of35and methyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-4-O-benzyl-α-L-rhamnopyranoside was selectively deacylated and condensed to 2-trichloroacetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl trichloroacetimidate to afford the corresponding fully protected tetrasaccharide45. Controlled stepwise deprotection of the latter proceeded smoothly to afford the target2. It should be emphasised that the preparation of45was not straightforward, several donors and coupling conditions that were tested resulted only in the complete recovery of the acceptor. Distortion of several signals in the13C NMR spectra of the fully or partially protected tetrasaccharide intermediates suggested that steric hindrance, added to the known low reactivity of HO-2 of rhamnosyl acceptors, probably played a major role in the outcome of the glycosidation attempts.
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