title: The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-D-glucuronides to L-iduronides are dependent on the anomeric substituent: syntheses and DFT calculations.
abstract: One of the shortest synthetic routes to L-iduronic acid derivatives is via free radical reduction of the C-5 bromide of the corresponding protected D-glucuronic acid derivative. The epimerization of such C-5 bromides to the L-ido derivatives via reaction with tributyltin hydride was investigated. It was found that the stereoselectivity of the reaction was dependent on the anomeric substituent. If the substituent was fluoride the L-ido product was obtained exclusively in 65-72% yield whereas the O-methyl or O-acetyl derivatives led to isomeric mixtures of both the L-ido and D-gluco products in different ratios depending on the reaction conditions. DFT calculations were performed to determine the stereoelectronic factors that favour formation of the L-ido isomer from the fluoride and suggest the selectivity is due to a transition state gauche effect and an Sn-F interaction.
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia. v.ferro@uq.edu.au e.krenske@uq.edu.au.
authors.forename: Shifaza
authors.initials: S
authors.lastname: Mohamed
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia. v.ferro@uq.edu.au e.krenske@uq.edu.au.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Krenske
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, QLD 4072, Australia. v.ferro@uq.edu.au e.krenske@uq.edu.au.
authors.forename: Vito
authors.initials: V
authors.lastname: Ferro
mesh_terms: D020719:Glucuronides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D014220:Trialkyltin Compounds / Q000737:chemistry*
chemical_list: D020719:Glucuronides; D014220:Trialkyltin Compounds; C011559:tributyltin