Studies on α-sialylation using sialyl donors with an auxiliary 3-thiophenyl group

Article abstract of DOI:10.1016/S0008-6215(97)00094-3

Reaction of the methyl ester of 2-chloro-3-S-phenyl-3-thiosialic acid (4) with sodium thiomethoxide in acetonitrile at 0°C affords the methyl ester of 2-S-methyl-3-S-phenyl-2,3-dithio-α-sialic acid (6a) in quantitative yield. Sialylation of tetrahydropyran-2-methanol (7) and 2-(trimethylsilyl)ethyl 2,2',3,6,6'-penta-O-benzyl-α-lactoside (8) with 6a in the presence of phenylsulfenyl triflate (PST) as promotor in CH₃CN at -40°C gives α-sialosides 9 and 10 in good yield and excellent stereoselectivity. No β-sialosides are formed in either case. Acetylation of product 10, and the subsequent reductive removal of the 3-thiophenyl group using Ph₃SnH, affords 12 - protected GM3 trisaccharide - in 82% yield after two steps. Sialylation of acceptor 8 with chloride 4 using silver triflate as promotor afforded 10 in 48% yield after two days at -15°C in THF. A possible mechanism of sialylation with 6a that involves intermediate α- and β-nitrilium ions is discussed.