Regioselective synthesis of a glycomimetic trisaccharide of Sialyl Lewis (sLe) |
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Authors: | Sameh E. Soliman Ramadan I. El-Sokkary Mina A. Nashed |
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Affiliation: | a Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, PO Box 426, Alexandria 21321, Egypt b Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada A1B 3V6 |
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Abstract: | Sialyl Lewis (sLex) is the smallest naturally occurring carbohydrate ligand that binds to E-Selectin on the activated endothelium. We report here the total synthesis of acetic acid-sLex analog (12), for testing as a therapeutic agent. Methoxyethyl 4-O-(3,4-O-isopropylidene-β-d-galactopyranosyl)-β-d-glucopyranoside (3) was prepared starting from the methoxyethyl-β-d-lactoside (2), which was selectively benzoylated to give the methoxyethyl 2,6-di-O-benzoyl-4-O-(2,6-di-O-benzoyl-3,4-O-isopropylidene-β-d-galactopyranosyl)-β-d-glucopyranoside (4). Glycosylation of acceptor 4 with methyl 2,3,4-tri-O-benzyl-1-thio-β-l-fucopyranoside (5) in the presence of cupric bromide and tetrabutylammonium bromide afforded the corresponding methoxyethyl 2,6-di-O-benzyl-3-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-4-O-(2,6-di-O-benzyl-3,4-O-isopropylidene-β-d-galactopyranosyl)-β-d-glucopyranoside (6). Selective removal of the 4″,6″-O-isopropylidene group from 6 gave the deprotected trisaccharide 7. The regioselective esterification of O-3″ of trisaccharide 8 (obtained from the dibutylstannylene derivative of 7) with benzyl-2-bromoacetate and tetrabutylammonium bromide afforded the 3″-O-carbobenzyloxymethyl trisaccharide derivative 9, which on saponification and hydrogenolysis with palladium-charcoal afforded the target trisaccharide 12 glycomimetic of Sialyl Lewis (sLex) trisaccharide omitting the sialic acid moiety. |
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Keywords: | Sialyl Lewis (sLex) Oligosaccharides Sialic acid bioisosters Substituted lactoside |
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