title: DFT studies of the ionization of alpha and beta glycopyranosyl donors.
abstract: Current attempts at mimicking the transition states (TSs) of glycosyl processing enzymes (GPEs) that proceed through TSs with a high degree of oxacarbenium ion formation suffer from a paucity of data about the conformations of such oxacarbenium ions. Because TSs are maxima, the current models based on minimized structures may need some refinement. As part of studies directed at optimizing chemical glycosylation the ionization of 3,4,6-tri-O-acetyl-alpha/beta-D-glucopyranosyl chlorides and triflates, 2,3,4,6-tetra-O-methyl-alpha/beta-D-glucopyranosyl fluorides, chlorides and triflates, 2,3,4,6-tetra-O-methyl-alpha/beta-D-mannopyranosyl fluorides, 2,3-di-O-methyl 4,6-O-benzylidene alpha/beta-D-mannopyranosyl triflates and 2,3-di-O-methyl 4,6-O-benzylidene alpha/beta-D-glucopyranosyl triflates was studied by a prototypic density functional theory (DFT) procedure. In all cases, the alpha-anomers ionized smoothly to 4H3 half chair conformations or adjacent envelopes. By contrast, all beta-anomers exhibited an abrupt conformational change before ionization was complete. The nature of the conformations sampled depends on both the leaving group and the protecting group. The methods presented can be readily adapted to the study of any GPE or chemical glycosylation and provide a method for initial evaluation of plausible TSs, which in turn can be used in mimetic design.
authors.affiliation: Institute for Biological Sciences, NRC Canada, 100 Sussex Drive, Ottawa, ON, Canada K1A 0R6. dennis.whitfield@nrc.ca
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Whitfield
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002712:Chlorides; D005459:Fluorides; D005960:Glucosides / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry*; D006031:Glycosylation; D007202:Indicators and Reagents; D007477:Ions; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry*
chemical_list: D002712:Chlorides; D005960:Glucosides; D006027:Glycosides; D007202:Indicators and Reagents; D007477:Ions; D009844:Oligosaccharides; D005459:Fluorides