SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .82. FIRST TOTAL SYNTHESIS OF SIALYL GLOBOPENTAOSYL CERAMIDE (V(3)NEU5ACGB(5)CER) AND ITS POSITIONAL ISOMER (V(6)NEU5ACGB(5)CER)

The first, total synthesis of sialyl globopentaosyl ceramide (V(3)Neu5 AcGb(5)Cer) and its positional isomer (V(6)Neu5AcGb(5)Cer) are describ ed. cc-Selective glycosylation of 2-(aimethylsilyi)ethyl -(1-->4)-2,3, 6-tri-O-benzyl-beta-D-glucopyranoside (7) with the suitably protected galactose donor, methyl -4,6-O-benzylidene-1-thio-beta-D-galactopyrano side gave the desired trisaccharide, which was transformed into the tr isaccharide acceptor, by removal of the O-acetyl group. Glycosylation of this acceptor with methyl -O-acetyl-4,6-0-benzylidene-2-deoxy-2-pht halimido- l-thio-p-D-galactopyranoside gave the globotetraose derivati ve, which was transformed into the acceptor 12 by removal of the phtha loyl and O-acetyl groups followed by N-acetylation. DMTST promoted cou pling of this acceptor with methyl O-(methyl -O-acetyl-3,5-dideoxy-D-g lycero-alpha-D-galacto-2- nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-b 1-thio-beta-D-galactopyranoside afforded the desired sialyl globopenta oside derivative in good yield, which was transformed, by removal of t he benzyl and benzylidene groups followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate fo rmation, into the final glycosyl donor 17. Condensation of this imidat e derivative with S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol ( 18) gave the beta-glycoside, which on channeling through selective red uction of the azido group, coupling of the amino group with octadecano ic acid, O-deacylation and saponification of the methyl ester group, g ave the title compound, sialyl globopentaosyl ceramide. The positional isomer was also obtained by coupling of the globotetraose acceptor wi th methyl O-(methyl -D-glycero-alpha-D-galacto-2-nonulopyranosylonate) -(2-->6)-2,4-di-O-benzoyl-3-O-benzyl-1- thio-beta-D-galactopyranoside , followed by essentially the same procedure employed for the synthesi s of sialyl globopentaosyl ceramide.