ISSN:
1573-4986
Keywords:
ganglioside GT1aα
;
sialic acid
;
cholinergic neuron-specific antigen
;
myelin-associated glycoprotein
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract An efficient total synthesis of a cholinergic neuron-specific ganglioside GT1aα (IV3NeuAcIII6NeuAcII3NeuAc-GgOse4Cer) is described. The suitably protected sialyl-α(2→6)-gangliotriose (III6NeuAc-GgOse3) derivative was glycosylated with the phenyl 2-thioglycoside of sialic acid in the presence of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) in acetonitrile medium, giving the disialogangliotriose (III6NeuAcII3NeuAc-GgOse3) derivative which contains both sialyl-α(2→6)-GalNAc and sialyl-α(2→3)-Gal structures (Route I). This pentasaccharide was efficiently synthesized also by the coupling of (methyl 5-acetamido-4,7,8,9-tetra-Ο-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→6)-2-deoxy-3,4-Ο-isopropylidene-2-phthalimido-D-galactopyranosyl trichloroacetimidate with 2-(trimethylsilyl)ethyl (methyl 5-acetamido-4,7,8,9-tetra-Ο-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-(2,6-di-Ο-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-Ο-benzyl-β-D-glucopyranoside, followed by conversion of the phthalimido group to the acetamido group (Route II). Ο-Deisopropylidenation and further glycosylation with methyl (methyl 5-acetamido-4,7,8,9-tetra-Ο-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-Ο-benzoyl-1-thio-β-D-galactopyranoside, promoted by dimethyl(methylthio)sulfonium triflate (DMTST), gave the desired trisialogangliotetraose (IV3NeuAcIII6NeuAcII3NeuAc-GgOse4) derivative, which was converted stepwise into the title ganglioside GT1aα by the introduction of the ceramide part and then complete deprotection. The ganglioside obtained was shown to be identical with the native GT1aα on TLC-immunostaining.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007020815583
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