Synthesis of an S-(alpha-sialosyl)-(2----9)-O-(alpha-sialosyl)-(2----3')-beta-lactos ylceramide.
A ganglioside GD3 analog has been synthesized having an N-acetylneuraminic acid (Neu5Ac) residue alpha-thioglycosidically linked to C-9 of the Neu5Ac residue in the ganglioside GM3 structure. Glycosylation of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-beta-D-galactopyranosyl)-(1----4)-2,6-di-O-benzoyl-beta-D -glucopyranoside with methyl (methyl 5-acetamido-4,7,8-tri-O-acetyl-9-bromo-3,5,9-trideoxy-D-glycero-alpha-D- galacto-2-nonulopyranosid)onate, which was prepared from methyl (methyl 5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2- nonulopyranosid)onate by 8,9-O-isopropylidenation, O-acetylation, hydrolysis of the isopropylidene group, selective bromination, and O-acetylation, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the alpha-sialosyl-(2----3')-lactoside 8. Coupling of the O-acetyl derivative of 8 with the sodium salt of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-alpha-D- galacto-2-nonulopyranosonate gave an alpha-thioglycosidically linked tetrasaccharide. This was converted, via selective removal of the 2-(trimethylsilyl)ethyl group, trichloroacetimidation, and glycosidation with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol into a ganglioside precursor. Finally the precursor on selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and de-esterification gave the analog, S-(N-acetyl-alpha-neuraminosyl)-(2----9)-O-(N-acetyl-9-thio-alpha- neuraminosyl)-(2----3')-beta-lactosylceramide.
Hasegawa
A
A
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Ogawa
H
H
Ishida
H
H
Kiso
M
M
D015703:Antigens, CD; D002240:Carbohydrate Sequence; D005732:Gangliosides / Q000737:chemistry*; D006028:Glycosphingolipids / Q000737:chemistry*; D007536:Isomerism; D007790:Lactosylceramides; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D012794:Sialic Acids / Q000737:chemistry*; D013865:Thioglycosides / Q000737:chemistry*
D015703:Antigens, CD; D005732:Gangliosides; D006028:Glycosphingolipids; D007790:Lactosylceramides; D012794:Sialic Acids; D013865:Thioglycosides; C009744:CDw17 antigen; C026226:ganglioside, GD3; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid