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-nonulopyranosonic acid (KDN) unit, have been synthesized. Methyl O-(methyl 4,5,7,8,9-penta- O-acetyl-3-deoxy- d- glycero-α- d- galacto-2-nonulopyranosylonate)-(2 → 3)-2,4,6-tri- O-benzoyl-1-thio-β- d-galactopyranoside ( 4) was prepared from 2-(trimethylsilyl)ethyl O-(methyl 4,5,7,8,9-penta- O-acetyl-3-deoxy- d- glycero-α- d- galacto-2-nonulopyranosylonate)-(2 → 3)-6- O-benzoyl-β- 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-β- d-glucopyranosyl)-(1 → 3)- O-(2,4,6-tri- O-benzyl-β- d-galactopyranosyl)-(1 → 4)-2,3,6-tri- O-benzyl-β- d-glucopyranoside ( 5) or of 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di- O-benzyl-2-deoxy-β- d-glucopyranosyl)-(1 → 3)- O-(2,4,6-tri- O-benzyl-β- d-galactopyranosyl)-(1 → 4)-2,3,6-tri- O-benzyl-β- 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-α- l-fucopyranosyl)-(1 → 3)- O-(2-acetamido-6- O-benzyl-2-deoxy-β- d-glucopyranosyl)-(1 → 3)- O-(2,4,6-tri- O-benzyl-β- d-galactopyranosyl)-(1 → 4)-2,3,6-tri- O-benzyl-β- 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 (2 S,3 R,4 E)-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 β-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.