title: The α-Glycosidation of Partially Unprotected N-Acetyl and N-Glycolyl Sialyl Donors in the Absence of a Nitrile Solvent Effect.
abstract: The synthesis of α-sialosides is one of the most difficult reactions in carbohydrate chemistry and is considered to be both a thermodynamically and kinetically disfavored process. The use of acetonitrile as a solvent is an effective solution for the α-selective glycosidation of N-acetyl sialic acids. In this report, we report on the α-glycosidation of partially unprotected N-acetyl and N-glycolyl donors in the absence of a nitrile solvent effect. The 9-O-benzyl-N-acetylthiosialoside underwent glycosidation in CH2 Cl2 with a good α-selectivity. On the other hand, the 4,7,8-O-triacetyl-9-O-benzyl-N-acetylthiosialoside was converted to β-sialoside as a major product under the same reaction conditions. The results indicate that the O-acetyl protection of the sialyl donor was a major factor in reducing the α-selectivity of sialylation. After tuning of the protecting groups of the hydroxy groups at the 4,7,8 position on the sialyl donor, we found that the 9-O-benzyl-4-O-chloroacetyl-N-acetylthiosialoside underwent sialylation with excellent α-selectivity in CH2 Cl2 . To demonstrate the utility of the method, straightforward synthesis of α(2,9) disialosides containing N-acetyl and/or N-glycolyl groups was achieved by using the two N-acetyl and N-glycolyl sialyl donors.
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H101 Ookayama, Meguro, Tokyo, 152-8552, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Aoyagi
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H101 Ookayama, Meguro, Tokyo, 152-8552, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohira
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H101 Ookayama, Meguro, Tokyo, 152-8552, Japan.|Laboratory of Chemical and Life Science, Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fuse
authors.affiliation: RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Uzawa
authors.affiliation: RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H101 Ookayama, Meguro, Tokyo, 152-8552, Japan. thiroshi@apc.titech.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000097:Acetonitriles; D000107:Acetylation; D006031:Glycosylation; D015394:Molecular Structure; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D012794:Sialic Acids / Q000737:chemistry*; D012997:Solvents; D013237:Stereoisomerism
chemical_list: D000097:Acetonitriles; D011134:Polysaccharides; D012794:Sialic Acids; D012997:Solvents; C032159:acetonitrile
keywords: acetonitrile; glycosylation; neuraminic acids; oligosaccharides; thioglycoside