Synthetic Studies on Sialoglycoconjugates 72: Synthesis of Sulfo-, Phosphono- and Sialyl-Lewis × Analogs Containing the 1-Deoxy- and 1,2-Dideoxy-hexopyranoses in Place of N-Acetylglucosamine Residue

Abstract

Sialyl-, sulfo- and phosphono-Le^x analogs containing 1-deoxy and 1,2-dideoxy-D-glucose in place of N-acetylglucosamine have been synthesized. Glycosylation of O-(2,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-galactopyranosyl)-(1→4)-1,5-anhydro-2,6-di-O-benzoyl-D-glucitol (5), prepared from per-O-lactose in five steps, or O-(2,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-galactopyranosyl)-(1→4)-1,5-anhydro-6-O-benzoyl-2-deoxy-D-arabino-hexitol(9), prepared from per-O-acetyllactal (2) in four steps, with the methyl 1-thioglycoside derivative of L-fucose, gave the corresponding trisacchrides 11 and 18. These are transformed into the glycosyl acceptors 12 and 19 for the sialyl Le^x analogs, and 15 and 22 for the sulfo- and phosphono Le^x analogs. Selective hydrolysis of the isopropylidene group of 11 and 18 yielded 12 and 19, respectively. The latter compounds were then converted to 15 and 22, respectively, by selective levulinylation, reductive removal of the benzyl groups followed by acetylation and removal of the levulinyl group. 15 and 22 were then converted in good yields, by sulfonation followed by O-deacylation, into the target compounds 17 and 24. Treatment of 22 with diphenyl chlorophosphate, and subsequent hydrogenolysis of the phenyl groups with Adams Platinum followed by O-deacylation afforded the phosphono-Le^x analog. Glycosylation of 12 or 19 with methyl (phenyl 5-acetamido4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate (27), using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH), afforded the desired tetrasaccharides, which were converted in good yields, via hydrogenolysis of the benzyl groups, O-acetylation, O-deacylation and deesterification into the sialyl Le^x analogs.