A Practical Method for the Synthesis of Sialyl α-Glycosides

Addition of 2,4-dimethylbenzenesulfenyl chloride to sialic acid glycal gives crystalline 2-chloro-3-thiosialic acid 3 in 85% yield. Reaction of 3 with sodium thiomethoxide in acetonitrile at 0 °C affords the sialic acid donor α-2-(methylthio)-3-thiosialic acid 4 in quantitative yield. Sialylation of glycosyl acceptors 9 and 10 with 4 in the presence of phenylsulfenyl triflate (PST) as promotor in CH3CN at −40 °C gives α-sialosides in good yield and excellent stereoselectivity. No β-sialosides are formed in either case. Removal of the auxiliary 3-(2,4-dimethylphenyl)thio group is achieved in high yield using Ph3SnH and AIBN in refluxing toluene. Protected GM3 trisaccharide and 6-sial-2-yllactose were obtained on a gram scale.