Synthesis of the methyl thioglycosides of deoxy- N-acetyl-neuraminic acids for use as glycosyl donors

Abstract

Methyl 2-thioglycoside derivatives of 4-, 7-, 8-, and 9-deoxy- N-acetylneuraminic acids have been prepared as glycosyl donors for the synthesis of sialoglycoconjates. Reduction of a (phenoxy)thiocarbonyl group, selectively introduced at the 4 position of methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-8,9- O-isopropylidene- d- glycero- α- d- galacto-2-nonulopyranosid]onate ( 1), gave the 4-deoxy compound, which was transformed via O-deisopropylidenation, acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, subsequent acetylation, and displacement of the 2-acetoxy group by a methylthio group, into methyl (methyl 5-acetamido-7,8,9-tri- O-acetyl-3,4,5-trideoxy-2-thio- d- manno-2-nonulopyranosid)onate ( 17). Methyl [2-(trimethylsilyl)ethyl 5-acetamido-8,9-di- O-acetyl-4- O-benzoyl-3,5,7-trideoxy-α- d- galacto-2- nonulopyranosid]onate, prepared from 1 in five steps, and methyl [2-(trimethylsilyl)ethyl 5-acetamido-4,7,9-tri- O-acetyl-3,5,8-trideoxy-α- d- galacto-2-nonulopyranosid]onate, prepared from 1 in six steps, were converted via selective removal of the 2-(trimethylsilyl)ethyl group, O-acetylation, and displacement of the 2-acetoxy group by a methylthio group as described for 17, into the corresponding methyl 7- and 8-deoxy-2-thioglycosides. Reductive dechlorination of methyl [2-(trimethylsilyl)ethyl 5-acetamido-4,7-di- O-benzoyl-9-chloro-3,5,9-trideoxy- d- glycero-α- d- galacto-2-nonulopyranosid]onate, prepared from methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy- d- glycero-α- d- galacto-2-nonulopyranosid]onate by selective 9- O- tert-butyldimethylsilylation, benzoylation, removal of the 9-silyl group, and selective chlorination, gave a 9-deoxy compound. This was transformed, via O-debenzoylation, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, 2- O-acetylation, 2-chlorination, displacement with potassium thioacetate, selective S-deacetylation, and S-methylation, into the methyl 2-thio-α-glycoside of 9-deoxy- N-acetylneuraminic acid.