A first total synthesis of a cholinergic neuron-specific ganglioside, GQ1bα (IV3Neu5Acα, III6Neu5Acα, II3Neu5Acα2-Gg4Cer) is described. Regio- and stereo-selective monosialylation of the hydroxyl group at C-6 of the GalNAc residue in 2-(trimethylsilyl)ethylO-(2-acetamido-2-deoxy-3,4-O-isopropylidene-β-d-galactopyranosyl)-(1→4)-O-(2,6-di-O-benzyl-β-dgalactopyranosyl)-(1→4)-O-2,3,6-tri-O-benzyl-β-dglucopyranoside (4) with methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-dglycero-dgalacto-2-nonulopyranosid) onate (5), and subsequent dimericsialylation of the hydroxyl group at C-3 of the Gal residue with methyl [phenyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-dglycero-α-dgalacto-2-nonulopyranosylono-1′,9-lactone)-4, 7-di-O-acetyl-3,5-dideoxy-2-thio-dglycero-dgalacto-2-nonulopyranosid]onate (7), usingN-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) as a promoter, gave the desired hexasaccharide8containing α-glycosidically-linked mono- and dimeric sialic acids. This was transformed into the acceptor9by removal of the isopropylidene group. Condensation of methylO-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-dglycero-α-dgalacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-dgalactopyranoside (10) with9, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the desired octasaccharide derivative11in high yield. Compound11was converted into α-trichloroacetimidate14,viareductive removal of the benzyl groups,O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (15), gave the β-glycoside16. Finally,16was transformed,viaselective reduction of the azido group, coupling with octadecanoic acid,O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside18in good yield.