A synthetic approach to polysialogangliosides containing alpha-sialyl-(2-->8)-sialic acid: total synthesis of ganglioside GD3.
A stereocontrolled, facile total synthesis of ganglioside GD3 is described as an example of a proposed systematic approach to the preparation of gangliosides containing an alpha-sialyl-(2-->8)-sialic acid unit alpha-glycosidically linked to O-3 of a D-galactose residue in their oligosaccharide chains. Glycosylation of 2-(trimethylsilyl)ethyl 6-O-benzoyl-, 3-O-benzoyl-, or 3-O-benzyl-beta-D-galactopyrano-sides, or 2-(trimethylsilyl)ethyl 2,3,6,2',6'-penta-O-benzyl-beta-lactoside (7), with methyl [phenyl 5- acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D- glycero-alpha-D-galacto-2-nonulopyranosylono-1',9 lactone)- 4,7-di-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyrano sid] onate (3), using N-iodosuccinimide-trifluoromethanesulfonic acid as a promoter, gave the corresponding alpha glycosides 8 (32%), 13 (33%), 14 (48%), and 17 (31%), respectively. The glycosyl donor 3 was prepared from O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosy lonic acid)-(2-->8)-5-acetamido-3,5- dideoxy-D-glycero-D-galacto-2-nonulopyranosonic acid by treatment with Amberlite IR-120 (H+) in methanol, O-acetylation, and subsequent replacement of the anomeric acetoxy group with phenylthio. Compound 8 was converted into the methyl beta-thioglycoside via O-benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group by reaction with methylthiotrimethylsilane. Compound 17 was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the alpha-trichloroacetimidate, which was coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol to give the beta-glycoside. This glycoside was easily transformed, via selective reduction of the azido group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester and lactone functions, into ganglioside GD3.
Ishida
H
H
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Ohta
Y
Y
Tsukada
Y
Y
Kiso
M
M
Hasegawa
A
A
D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000737:chemistry*; D005732:Gangliosides / Q000138:chemical synthesis*; D006027:Glycosides / Q000737:chemistry; D006031:Glycosylation; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D012794:Sialic Acids / Q000737:chemistry*; D013237:Stereoisomerism; D013865:Thioglycosides / Q000737:chemistry
D004187:Disaccharides; D005732:Gangliosides; D006027:Glycosides; D012794:Sialic Acids; D013865:Thioglycosides; C026226:ganglioside, GD3; D019158:N-Acetylneuraminic Acid