Regioselective synthesis of a glycomimetic trisaccharide of Sialyl Lewis (sLex).
Sialyl Lewis (sLe(x)) 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-sLe(x) analog (12), for testing as a therapeutic agent. Methoxyethyl 4-O-(3,4-O-isopropylidene-beta-D-galactopyranosyl)-beta-D-glucopyranoside (3) was prepared starting from the methoxyethyl-beta-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-beta-D-galactopyranosyl)-beta-D-glucopyranoside (4). Glycosylation of acceptor 4 with methyl 2,3,4-tri-O-benzyl-1-thio-beta-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-alpha-L-fucopyranosyl)-4-O-(2,6-di-O-benzyl-3,4-O-isopropylidene-beta-D-galactopyranosyl)-beta-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 (sLe(x)) trisaccharide omitting the sialic acid moiety.
Soliman
Sameh E
SE
Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, PO Box 426, Alexandria 21321, Egypt.
Bassily
Rafik W
RW
El-Sokkary
Ramadan I
RI
Banoub
Joseph
J
Nashed
Mina A
MA
D019342:Acetic Acid / Q000737:chemistry; D032701:Biomimetics; D015195:Drug Design; D006031:Glycosylation; D009844:Oligosaccharides / Q000737:chemistry*; D000080506:Sialyl Lewis X Antigen; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D014312:Trisaccharides / Q000138:chemical synthesis / Q000737:chemistry*
D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D014312:Trisaccharides; D019342:Acetic Acid