Synthesis of chemically modified sialic acid-containing sialyl-LeX ganglioside analogues recognized by the selectin family.
Sialyl Lewis X ganglioside analogues containing 5-acetamido-3,5-dideoxy-L-arabino-2-heptulopyranosylonic acid (C7-Neu5Ac), 5-acetamido-3,5-dideoxy-D-galacto-2-octulopyranosylonic acid (C8-Neu5Ac), and 5-acetamido-3,5-dideoxy-L-glycero-D-galacto-1-2-nonulopyranosylonic++ + acid (8-epi-Neu5Ac) in place of N-acetylneuraminic acid (Neu5Ac) have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl 6-O-benzoyl-beta-D-galactopyranoside with the phenyl or methyl 2-thioglycoside derivatives of the respective sialic acids, using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid as a promoter in acetonitrile, gave the three required 2-(trimethylsilyl)ethyl (2S)-sialyl-(2-->3)-beta-galactopyranosides. These were converted via O-benzoylation, selective transformation of the 2-(trimethylsilyl)ethyl group to acetyl, and introduction of the methylthio group with methylthiotrimethylsilane into the corresponding glycosyl donors. Glycosylation of 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 with these donors in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) afforded the expected beta-glycosides, which were converted into the corresponding alpha-trichloroacetimidates, and these, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol, gave the required beta-glycosides. Finally, these were transformed via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and de-esterification into the target compounds in good yields.
Yoshida
M
M
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Uchimura
A
A
Kiso
M
M
Hasegawa
A
A
D002240:Carbohydrate Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology*; D019040:E-Selectin; D006031:Glycosylation; D019041:L-Selectin; D016256:Lewis X Antigen / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000276:immunology; D012794:Sialic Acids / Q000032:analysis*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016256:Lewis X Antigen; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D012794:Sialic Acids; D019041:L-Selectin; D019158:N-Acetylneuraminic Acid