title: Vibrational circular dichroism spectroscopy study of paroxetine and femoxetine precursors.
abstract: The solution structures of (3R,4S)- and (3S,4R)- 4-(4-fluorophenyl)-3-hydroxylmethyl- 1-methylpiperidine, which are intermediates in the synthesis of the two pharmaceuticals paroxetine and femoxetine, were studied by vibrational circular dichroism (VCD) spectroscopy. In addition, six derivatives with different substituents attached to the C3 atom were prepared and their VCD and absorption spectra discussed with the aid of ab initio simulations. The VCD spectra were found to be sensitive to the geometry changes. In addition, a subtle variation caused by intermolecular aggregation was apparent in the spectra. The VCD technique can be applied for structural analysis of chiral pharmaceuticals in solutions.
authors.affiliation: Department of Physics and Measurements, Institute of Chemical Technology, Technická 5, 166 28 Praha 6, Czech Republic. marie.urbanova@vscht.cz
authors.forename: Marie
authors.initials: M
authors.lastname: Urbanová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Setnicka
authors.forename: Petr
authors.initials: P
authors.lastname: Bour
authors.forename: Hana
authors.initials: H
authors.lastname: Navrátilová
authors.forename: Karel
authors.initials: K
authors.lastname: Volka
mesh_terms: D002942:Circular Dichroism; D008956:Models, Chemical; D017374:Paroxetine / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry*
chemical_list: D017374:Paroxetine; D010880:Piperidines; D017367:Selective Serotonin Reuptake Inhibitors; C010655:femoxetine