title: C2-Oxyanion Neighboring Group Participation: Transition State Structure for the Hydroxide-Promoted Hydrolysis of 4-Nitrophenyl α-d-Mannopyranoside.
abstract: The hydroxide-catalyzed hydrolysis of aryl 1,2-trans-glycosides proceeds through a mechanism involving neighboring group participation by a C2-oxyanion and rate-limiting formation of a 1,2-anhydro sugar (oxirane) intermediate. The transition state for the hydroxide-catalyzed hydrolysis of 4-nitrophenyl α-d-mannopyranoside in aqueous media has been studied by the use of multiple kinetic isotope effect (KIE) measurements in conjunction with ab initio theoretical methods. The experimental KIEs are C1-2H (1.112 ± 0.004), C2-2H (1.045 ± 0.005), anomeric 1-13C (1.026 ± 0.006), C2-13C (0.999 ± 0.005), leaving group oxygen 2-18O (1.040 ± 0.012), and C2-18O (1.044 ± 0.006). The transition state for the hydrolysis reaction was modeled computationally using the experimental KIE values as constraints. Taken together, the reported kinetic isotope effects and computational modeling are consistent with the reaction mechanism involving rate-limiting formation of a transient oxirane intermediate that opens in water to give α-d-mannopyranose. The transition state has significant nucleophilic participation by the C2-alkoxide, an essentially cleaved glycosidic bond, and a slight shortening of the endocyclic C1-O5 bond. The TS is late, consistent with the large, normal C2-18O isotope effect.
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne , 30 Flemington Road, Parkville, Victoria 3010, Australia.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Speciale
authors.affiliation: Department of Chemistry, Simon Fraser University , 8888 University Drive, Burnaby, B.C. V5A 1S6, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Farren-Dai
authors.affiliation: Department of Chemistry, Simon Fraser University , 8888 University Drive, Burnaby, B.C. V5A 1S6, Canada.
authors.forename: Fahimeh S
authors.initials: FS
authors.lastname: Shidmoossavee
authors.affiliation: School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne , 30 Flemington Road, Parkville, Victoria 3010, Australia.
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Williams
authors.affiliation: Department of Chemistry, Simon Fraser University , 8888 University Drive, Burnaby, B.C. V5A 1S6, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bennet
mesh_terms: D003903:Deuterium / Q000737:chemistry; D006868:Hydrolysis; D006878:Hydroxides / Q000737:chemistry*; D007700:Kinetics; D008358:Mannose / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009596:Nitrophenols / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D010103:Oxygen Isotopes / Q000737:chemistry
chemical_list: D006878:Hydroxides; D009596:Nitrophenols; D010103:Oxygen Isotopes; C000615259:Oxygen-18; C024719:4-nitrophenyl; D003903:Deuterium; D008358:Mannose; D010100:Oxygen