SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .52. SYNTHESIS OF SIALYL LEWIS-X ANALOGS CONTAINING AZIDOALKYL GROUPS AT THE REDUCING END

Stereocontrolled synthesis of sialyl Le(x) epitope analogs in which the terminal N-acetylglucosamine residue of sialyl Le(x) determinant is replaced by a D-glucopyranose residue containing beta-glycosidically linked azidoalkyl groups is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2,6-di-O-benzoyl-3,4-0-isopropylidene-beta-D-galactopyranosyl)-(1-->4)-2,6-di-O-benzoyl-beta-D-glucopyranoside (2), prepared from 2-(trimethylsilyl)ethyl beta-lactoside (1) by 3,4-0-isopropylidenation and selective-0-benzoylation, with methyl 2,3,4-tri-O-benzyl-1-thio-5-L-fucopyranoside (3) gave the desired alpha-glycoside 4, which was converted by O-deisopropylidenation into 7, and via 0-debenzoylation, selective 2,6,6'-tri-O-benzoylation and O-deisopropylidenation into 8, respectively. N-Iodosuccinimide (NIS)-TfOH-promoted glycosylation of 7 or 8 with methyl (phenyl 5-acetamido-4,7,8,9-tetra-0-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate (9) afforded the desired tetrasaccharides 10 and 11. Compound 11 was converted into the alpha-trichloroacetimidate 14 via reductive removal of the benzyl groups, 0-acetylation, removal of the 2-(trimethylsilyl)ethyl group and treatment with trichloroacetonitrile. Coupling of 14 with 2-azidoethanol, 8-azidooctanol, and 2-[2-(2-azidoethoxy)ethoxy]ethanol, gave the desired 5-glycosides 15-17, respectively. O-Deacylation of 12, 15-17 and subsequent hydrolysis of the methyl ester group yielded the title compounds.