Total synthesis of VIM-2 ganglioside isolated from human chronic myelogenous leukemia cells

Article abstract of DOI:10.1016/0008-6215(95)00353-3

A total synthesis of the tumor-associated glycolipid antigen, VIM-2. is described. Phenyl 2,3,4-tri-O-benzoyl-6-O-benzyl-β-D-galactopyranosyl-(1 → 4)-6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (7), a key intermediate prepared by condensation of phenyl 6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (6) and 2,3,4-tri-O-benzoyl-6-O-benzyl-α-D-galactopyranosyl bromide (5), was glycosylated with methyl 2,3,4-tri-O-benzyl-1-thio-β-L-fucopyranoside (8) to give the trisaccharide donor 9, which, on coupling with 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranosyl-(1 → 4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (10), afforded the pentasaccharide 11. The regioselective glycosylation of 12 (derived by O-debenzoylation of 11) with 7 gave the heptasaccharide 13, which was converted by treatment with hydrazine monohydrate and subsequent N-acetylation into the hexasaccharide acceptor 14. The stereo- and regio-selective glycosylation of 14 with methyl (phenyl 5-acetamido-4,7,8,9-O-benzoyl-3,5-dideoxy-2-thio-D-glycero-β-D-galact o-2-nonulopyranosid)onate (16) gave the desired octasaccharide 18. Hydrogenolytic removal of the benzyl groups in 18 and successive O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile gave the α-trichloroacetimidate 21, which was then coupled with (2S,3R,4E)-2-azido-3-O-(tert-butyldiphenylsilyl)4-octadecene-1,3-diol (22) to give 23. Compound 23 was transformed, via selective reduction of the azido group, N-introduction of octadecanoic acid, O-desilylation, O-deacylation, and saponification of the methyl ester group, into the title VIM-2 ganglioside 26.