Synthesis of KDN-lactotetraosylceramide, KDN-neolactotetraosylceramide, and KDN-Lewis X ganglioside.
Analogues of sialyl-lactotetraosylceramide, sialyl-neolactotetraosylceramide, and sialyl Lewis X ganglioside, in which the N-acetylneuraminic acid residue is replaced by a 3-deoxy-D-glycero-D-galacto-2-nonulopyranosylonic acid (KDN) unit, have been synthesized. Methyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-alpha-D-galacto-2- nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-beta-D- galactopyranoside (4) was prepared from 2-(trimethylsilyl)ethyl O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-alpha-D-galacto-2- nonulopyranosylonate)-(2-->3)-6-O-benzoyl-beta-D-galactopyranoside , via O-benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group with trimethyl(methylthio)silane. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl)-(1-->3)- O- (2,4,6-tri-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl- beta- D-glucopyranoside (5) or of 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranosyl)-(1-->3)-O- (2,4,6-tri-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl- beta- D-glucopyranoside, prepared from 5 via O-benzylation and reductive opening of the benzylidene acetal ring, with 4 as a donor gave the corresponding pentasaccharides 9 and 13 in good yields. In the same way, 4 was reacted 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)-O-(2,4,6-tri-O-benzyl-be ta- D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside to yield the hexasaccharide 17. These three oligosaccharides 9, 13, and 17 were converted via reductive removal of the benzyl groups and benzylidene group, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and subsequent reaction with trichloroacetonitrile, into the corresponding trichloroacetimidates 12, 16, and 20, respectively. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 12, 16, and 20 in the presence of boron trifluoride etherate afforded the expected beta-glycosides, which were transformed via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and de-esterification, into the target gangliosides in high yields.
Terada
T
T
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Kiso
M
M
Hasegawa
A
A
D002240:Carbohydrate Sequence; D005732:Gangliosides / Q000138:chemical synthesis*; D006028:Glycosphingolipids / Q000138:chemical synthesis*; D016256:Lewis X Antigen; D008969:Molecular Sequence Data
D005732:Gangliosides; D006028:Glycosphingolipids; C088735:KDN-Lewis X ganglioside; C088736:KDN-lactotetraosylceramide; C088737:KDN-neolactotetraosylceramide; D016256:Lewis X Antigen