title: Dissecting the mechanisms of a class of chemical glycosylation using primary ¹³C kinetic isotope effects.
abstract: Although arguably the most important reaction in glycoscience, chemical glycosylations are among the least well understood of organic chemical reactions, resulting in an unnecessarily high degree of empiricism and a brake on rational development in this critical area. To address this problem, primary (13)C kinetic isotope effects have now been determined for the formation of β- and α-manno- and glucopyranosides using a natural abundance NMR method. In contrast to the common current assumption, for three of the four cases studied the experimental and computed values are indicative of associative displacement of the intermediate covalent glycosyl trifluoromethanesulfonates. For the formation of the α-mannopyranosides, the experimentally determined KIE differs significantly from that computed for an associative displacement, which is strongly suggestive of a dissociative mechanism that approaches the intermediacy of a glycosyl oxocarbenium ion. The application of analogous experiments to other glycosylation systems should shed further light on their mechanisms and thus assist in the design of better reactions conditions with improved stereoselectivity.
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de Terrasse, 91198 Gif-sur-Yvette, France.
authors: Min
authors: M
authors: Huang
authors: Graham E
authors: GE
authors: Garrett
authors: Nicolas
authors: N
authors: Birlirakis
authors: Luis
authors: L
authors: Bohé
authors: Derek A
authors: DA
authors: Pratt
authors: David
authors: D
authors: Crich
mesh_terms: D002247:Carbon Isotopes; D006031:Glycosylation; D007700:Kinetics; D008358:Mannose / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011789:Quantum Theory
chemical_list: D002247:Carbon Isotopes; D008358:Mannose