Synthesis of deoxygalactose-containing sialyl Le(X) ganglioside analogues to elucidate the structure necessary for selectin recognition.
Sialyl Lewis X ganglioside analogues containing 4-deoxy-, 6-deoxy-, and 4,6-dideoxy-D-galactopyranose in place of D-galactopyranose have been synthesized. Glycosylations of 2-(trimethylsilyl)ethyl 2,6-di-O-benzyl-beta-D-galactopyranoside and 2-(trimethylsilyl)ethyl beta-D-fucopyranoside with the phenyl 2-thioglycoside derivative of sialic acid, using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) as the promoter in acetonitrile, gave the desired 2-(trimethylsilyl)ethyl sialyl-alpha-2-->3)-beta-D-galactopyranoside and -beta-D-fucopyranoside, respectively. The sialylgalactose derivative obtained was then modified to 4-deoxy and 4,6-dideoxy derivatives. These were converted, by O-benzoylation, transformation of the 2-(trimethylsilyl)ethyl group to trichloroacetimidates, and introduction of the methylthio group with methylthiomethylsilane, into the corresponding glycosyl donors, which were then coupled with 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-(1->3)-O-(2-acetamido-6-O- benzyl-2-deoxy-beta-D-glucopyranosyl)-(1->3)-2,4,6-tri-O-benzyl-beta-D- galactopyranoside in the presence of dimethyl(methylthio)sulfonium triflate (DMTST). The resulting pentasaccharides were each converted to the corresponding alpha-trichloroacetimidates, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol, gave the desired sphingosine derivatives. Selective reduction of the azide group, N-acylation with octadecanoic acid, O-deacylation, and saponification of the methyl ester afforded the target compounds.
Komba
S
S
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Ishida
H
H
Kiso
M
M
Hasegawa
A
A
D000818:Animals; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005643:Fucose; D006031:Glycosylation; D006801:Humans; D007202:Indicators and Reagents; D016256:Lewis X Antigen / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D009904:Optical Rotation; D019087:Selectins / Q000737:chemistry / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D013055:Spectrophotometry, Infrared
D007202:Indicators and Reagents; D016256:Lewis X Antigen; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D005643:Fucose