title: Stereochemistry of the Brivaracetam Diastereoisomers.
abstract: The stereochemistry of all four stereoisomers of brivaracetam was determined using vibrational circular dichroism (VCD) spectroscopy. By comparing experimentally obtained VCD spectra and computationally simulated ones, the absolute configurations can be confidently assigned without prior knowledge of their relative stereochemistry. Neither the corrected mean absolute errors analysis of the nuclear magnetic resonance (NMR) data, nor the matching of experimental and calculated infrared spectra allowed the diastereoisomers to be distinguished. VCD spectroscopy itself suffices to establish the absolute configurations of all diastereoisomers. The relative stereochemistry could also be statistically confirmed by matching experimental and computed NMR spectra using the CP3 algorithm. The combination of VCD and NMR is recommended for molecules bearing more than one chiral center, as the relative configurations obtained from NMR serve as an independent check for those established with VCD. Analysis of the calculated VCD spectra reveals that the localized NH2 scissoring mode at around 1600 cm(-1) is characteristic for intramolecular hydrogen bonding, while the orientation of the ethyl group is reflected by the delocalized modes between 1150 and 1050 cm(-1).
authors.affiliation: Department of Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Shi
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Department of Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Kourosch Abbaspour
authors.initials: KA
authors.lastname: Tehrani
authors.affiliation: Department of Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Sergey
authors.initials: S
authors.lastname: Sergeyev
authors.affiliation: Department of Inorganic and Physical Chemistry, Ghent University, Ghent, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bultinck
authors.affiliation: Department of Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Herrebout
authors.affiliation: UCB Pharma, Braine-L'Alleud, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Mathieu
mesh_terms: D002942:Circular Dichroism; D004980:Ethane / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011760:Pyrrolidinones / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D011760:Pyrrolidinones; D004980:Ethane; C482793:brivaracetam
keywords: marker bands for intramolecular hydrogen bond; randomization plot; similarity indices; vibrational circular dichroism (VCD)