Synthesis of sialyl Lewis X ganglioside analogues containing modified L-fucose residues.
Sialyl Le(x) ganglioside analogues containing 2-epi-, 2,3-di-epi-, 4-epi-, and 2-O-methyl-L-fucose in place of the L-fucose residue have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl)-(1-->3)- 2,4,6- tri-O-benzyl-beta-D-galactopyranoside with the methyl 1-thioglycoside derivatives of the respective fucose analogues, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the corresponding protected 2-(trimethylsilyl)ethyl deoxy-alpha-L-hexopyranosyl-(1-->3)-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1-->3)-beta-D-galactopyrano sid es. These were transformed by reductive ring-opening of their benzylidene acetal groups into the glycosyl acceptors. Dimethyl (methylthio)sulfonium triflate-promoted glycosylation of these compounds with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2- nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-beta-D- galactopyranoside afforded the desired pentasaccharides, which were converted via reductive removal of their benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the corresponding alpha-tri-chloroacetimidates. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol these in the presence of boron trifluoride etherate afforded the expected beta-glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and deesterification, into the target gangliosides. The 2-(trimethylsilyl)ethyl glycosides of sialyl Le(x) oligosaccharides containing modified fucose were also prepared from the intermediates of the ganglioside synthesis.
Hasegawa
A
A
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Kato
M
M
Ando
T
T
Ishida
H
H
Kiso
M
M
D002240:Carbohydrate Sequence; D005643:Fucose / Q000032:analysis*; D005732:Gangliosides / Q000138:chemical synthesis* / Q000737:chemistry*; D007983:Lewis Blood Group Antigens / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
D005732:Gangliosides; D007983:Lewis Blood Group Antigens; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; C094688:sialyl Lewis(x) ganglioside; D005643:Fucose