title: Is an acyl group at O-3 in glucosyl donors able to control α-stereoselectivity of glycosylation? The role of conformational mobility and the protecting group at O-6.
abstract: The stereodirecting effect of a 3-O-acetyl protecting group, which is potentially capable of the remote anchimeric participation, and other protecting groups in 2-O-benzyl glucosyl donors with flexible and rigid conformations has been investigated. To this aim, an array of N-phenyltrifluoroacetimidoyl and sulfoxide donors bearing either 3-O-acetyl or 3-O-benzyl groups in combination with 4,6-di-O-benzyl, 6-O-acyl-4-O-benzyl, or 4,6-O-benzylidene protecting groups was prepared. The conformationally flexible 3-O-acetylated glucosyl donor protected at other positions with O-benzyl groups demonstrated very low or no α-stereoselectivity upon glycosylation of primary or secondary acceptors. On the contrary, 3,6-di-O-acylated glucosyl donors proved to be highly α-stereoselective as well as the donor having a single potentially participating acetyl group at O-6. The 3,6-di-O-acylated donor was shown to be the best α-glucosylating block for the primary acceptor, whereas the best α-selectivity of glycosylation of the secondary acceptor was achieved with the 6-O-acylated donor. Glycosylation of the secondary acceptor with the conformationally constrained 3-O-acetyl-4,6-O-benzylidene-protected donor displayed under standard conditions (-35°C) even lower α-selectivity as compared to the 3-O-benzyl analogue. However, increasing the reaction temperature essentially raised the α-stereoselectivities of glycosylation with both 3-O-acetyl and 3-O-benzyl donors and made them almost equal. The stereodirecting effects of protecting groups observed for N-phenyltrifluoroacetimidoyl donors were also generally proven for sulfoxide donors.
authors.affiliation: Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia.
authors.forename: Bozhena S
authors.initials: BS
authors.lastname: Komarova
authors.affiliation: Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Orekhova
authors.affiliation: Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia.
authors.forename: Yury E
authors.initials: YE
authors.lastname: Tsvetkov
authors.affiliation: Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russia. Electronic address: nen@ioc.ac.ru.
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
mesh_terms: D002236:Carbohydrate Conformation; D006031:Glycosylation; D007096:Imidoesters / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry; D012451:Safrole / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D007096:Imidoesters; D009844:Oligosaccharides; D012451:Safrole; C005746:sulfoxide
keywords: 3-O-Acetyl group; Glucosyl N-phenyltrifluoroacetimidate; Glucosyl sulfoxide; Glycosylation; Remote anchimeric participation; α-Stereodirecting effect