Systematic synthesis of α-sialyl-(2 → 3)- and -(2 → 6)-isoglobopentaosylceramides (V3 Neu5AciGb5Cer and V6Neu5AciGb5Cer)

Systematic syntheses of the isoglobo-series gangliosides, α-sialyl-(2 → 3)- and -(2 → 6)-isoglobopentaosyl ceramides (21 and 24, V3Neu5AciGb5Cer and V6Neu5AciGb5Cer) are described. 2-(Trimethylsilyl)ethyl 2-O-benzyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1 → 3)2,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (4), the core structure of the isoglobo-series gangliosides was prepared by the glycosylation of 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (2) with methyl 3-O-acetyl-2-O-benzyl-4,6-O-benzylidene-1-thio-β-d-galactopyranoside (1), and subsequent O-deacetylation. Coupling of 4 and methyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-β-d-galactopyranoside gave an isoglobotetraoside derivative 6, from which the phthaloyl and O-acetyl groups were removed. N-Acetylation then gave a tetrasaccharide acceptor 7. Dimethyl(methylthio)sulfonium triflate-promoted coupling of 7 with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto)-(2 → 3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside or -(2 → 6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-β-d-galactopyranoside gave the pentasaccharide derivative 9 and 14 in good yields. Compounds 9 and 14 were converted into the corresponding α-trichloroimidates 12 and 17 which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18), gave the β-glycoside 19 and 22, respectively. Finally, 19 and 22 were transformed, via selective reduction of azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group into 21 and 24, respectively.