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

A total synthesis of the tumor associated glycolipid antigen, VIM-2, is described [2]. 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- glucopyranoside7), a key intermediate prepared by condensation of phenyl 6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-d- glucopyranoside (bd6) and 2,3,4-tri-O-benzoyl-6-O-benzyl-α-d-galacotopyranosyl bromide (bd5), ws glycosylated with methyl 2,3,4-tri-O-benzyl-1-thio-b-1-fucopyranoside (bd8) to give the trisaccharide donor bd9, which on coupling with 2-(trimethysily)ethyl 2,46-tri-O-benzyl-b-d-galactopyranosyl-1-(1 → 4)-2,3->tri-O-benzyld-glucopyranoside (bd10), afforded the pentasaccharide 11. The regioselective glycosylation of 12 (derived by O-debenzoylation of 11) with 7 gave the heptassacharide 13, which was converted by treatment with hydrazine monohydrate and subsequent N-acetylation into the hexasaccharide acceptor 14. The stereo- and regio-selective glycosilation of 14 with methyl (phenyl5-acetamido-4,7,8,9-O-benzoyl-3,5-dideoxy-2- thio-d-glycerob-d-galacto-2-nonulopyranosid (bd16) gave the desired octasaccharide 18. Hydrogenolytic removal of the benzyl groups in 18 and successive O-acetylation, removal of the 2-(trimethylsily)ethyl group, and treatment with trichloroacetonitrile gave the α-trichloroacetimidate 21, which was then coupled with (2S,3R,4E)-2-azido-3-O-(tert-butyldiphenysilyl)-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-desiylation, O-deacylation, and saponification of the metyl ester group, into the titile VIM-2- ganglioside 26.