title: Studies on alpha-sialylation using sialyl donors with an auxiliary 3-thiophenyl group.
abstract: 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.
authors.affiliation: Department of Chemistry, Harvard University, Cambridge, MA 02138, USA.
authors.forename: V
authors.initials: V
authors.lastname: Martichonok
authors.forename: G M
authors.initials: GM
authors.lastname: Whitesides
mesh_terms: D002240:Carbohydrate Sequence; D006027:Glycosides / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry*; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D006027:Glycosides; D012794:Sialic Acids; C108413:methyl 2-S-methyl-3-S-phenyl-2,3-dithio-alph-sialate; D019158:N-Acetylneuraminic Acid