Synthetic Studies on Sialoglycoconjugates 52: Synthesis of Sialyl Lewis X Analogs Containing Azidoalkyl Groups at the Reducing End

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Abstract
Stereocontrolled synthesis of sialyl Lex epitope analogs in which the terminal N-acetylglucosamine residue of sialyl Lex determinant is replaced by a D-glucopyranose residue containing β-glycosidically linked azidoalkyl groups is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-galactopyra-nosyl)-(1→4)-2,6-di-O-benzoyl-β-D-glucopyranoside (2), prepared from 2-(trimethylsi-lyl)ethyl β-lactoside (1) by 3,4-O-isopropylidenation and selective-O-benzoylation, with methyl 2,3,4-tri-O-benzyl-l-thio-β-L-fucopyranoside (3) gave the desired a-glycoside 4, which was converted by O-deisopropylidenation into 7, and via O-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-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyra-nosid)onate (9) afforded the desired tetrasaccharides 10 and 11. Compound 11 was converted into the α-trichloroacetimidate 14 via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group and treatment with trichloroacetonitrile. Coupling of 14 with 2-azidoethanol, 8-azidooc-tanol, and 2-[2-(2-azidoethoxy)ethoxy]ethanol, gave the desired β-glycosides 15-17, respectively. O-Deacylation of 12, 15-17 and subsequent hydrolysis of the methyl ester group yielded the tide compounds.