The first, total synthesis of sialyl globopentaosyl ceramide (V3Neu5AcGb5Cer) and its positional isomer (V6Neu5AcGb5Cer) are described. α-Selective glycosylation of 2-(trimethylsilyl)ethylO-(2,3,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (7) with the suitably protected galactose donor, methyl 3-O-acetyl-2-O-benzyl-4,6-O-benzylidene-l-thio-β-D-galactopyranoside gave the desired trisaccharide, which was transformed into the trisaccharide acceptor, by removal of theO-acetyl group. Glycosylation of this acceptor with methyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-l-thio-β-D-galactopyranoside gave the globotetraose derivative, which was transformed into the acceptor12by removal of the phthaloyl andO-acetyl groups followed byN-acetylation. DMTST promoted coupling of this acceptor with methylO-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-l-thio-β-D-galactopyranoside afforded the desired sialyl globopentaoside derivative in good yield, which was transformed, by removal of the benzyl and benzylidene groups followed byO-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the final glycosyl donor17. Condensation of this imidate derivative with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18) gave the β-glycoside, which on channeling through selective reduction of the azido group, coupling of the amino group with octadecanoic acid,O-deacylation and saponification of the methyl ester group, gave the title compound, sialyl globopentaosyl ceramide. The positional isomer was also obtained by coupling of the globotetraose acceptor with methylO-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-β-D-galactopyranoside, followed by essentially the same procedure employed for the synthesis of sialyl globopentaosyl ceramide.