SYSTEMATIC SYNTHESIS OF ALPHA-SIALYL-(2-]3)-ISOGLOBOPENTAOSYLCERAMIDEAND ALPHA-SIALYL-(2-]6)-ISOGLOBOPENTAOSYLCERAMIDE (V(3)NEU5ACIGB(5)CER AND V(6)NEU5ACIGB(5)CER)

Systematic syntheses of the isoglobo-series gangliosides, alpha-sialyl -(2-->3)- and -(2-->6)-isoglobopentaosyl ceramides (21 and 24, V(3)Neu 5AciGb(5)Cer and V(6)Neu5AciGb(5)Cer) are described. 2-(Trimethylsilyl )ethyl 4,6-O-benzylidene-alpha-D-galactpyranosyl-(1-->3)- -(1-->4)-2,3 ,6-tri-O-benzyl-beta-D-glucopyranoside (4), the core structure of the isoglobo-series gangliosides was prepared by the glycosylation of 2-(t rimethylsilyl)ethyl -(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (2) with methyl -4,6-O-benzylidene-1-thio-beta-D-galactopyranoside (1 ), and subsequent O-deacetylation. Coupling of 4 and methyl -acetyl-4, 6-O-benzylidene-2-deoxy-2-phthalimido-1- thio-beta-D-galactopyranoside gave an isoglobotetraoside derivative 6, from which the phthaloyl and O-acetyl groups were removed. N-Acetylation then gave a tetrasacchari de acceptor 7. Dimethyl(methylthio)sulfonium triflate-promoted couplin g of 7 with methyl (methyl ,4,6-tri-O-benzoyl-1-thio-beta-D-galactopyr anoside or benzoyl-3-O-benzyl-1-thio-beta-D-galactopyranoside gave the pentasaccharide derivative 9 and 14 in good yields, Compounds 9 and 1 4 were converted into the corresponding alpha-trichloroimidates 12 and 17 which, on coupling with S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene- 1,3-diol (18), gave the beta-glycoside 19 and 22, respectively, Finall y, 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, (C) 1996 Elsevie r Science Ltd.