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

Reaction of the methyl ester of 2-chloro-3-S-phenyl-3-thiosialic acid (4) with sodium thiomethoxide in acetonitrile at 0 degrees C affords the methyl ester of 2-S-methyl-3-S-phenyl-2,3-di-thio-alpha-sialic acid (6a) in quantitative yield. Sialylation of tetrahydropyran-2-methanol (7) and 2-(trimethylsilyl)ethyl 2,2'3,6,6'-penta-O-benzyl-alpha-lactoside (8) with 6a in the presence of phenylsulfenyl triflate (PST) as promotor in CH3 CN at -40 degrees C gives alpha-sialosides 9 and 10 in good yield and excellent stereoselectivity. No beta-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 degrees C in THF. A possible mechanism of sialylation with 6a that involves intermediate alpha- and beta-nitrilium ions is discussed.