Premium
Stereochemistry of the Brivaracetam Diastereoisomers
Author(s) -
Qiu Shi,
Tehrani Kourosch Abbaspour,
Sergeyev Sergey,
Bultinck Patrick,
Herrebout Wouter,
Mathieu Benoit
Publication year - 2016
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22558
Subject(s) - chemistry , diastereomer , vibrational circular dichroism , absolute configuration , spectroscopy , intramolecular force , spectral line , two dimensional nuclear magnetic resonance spectroscopy , chemical shift , stereochemistry , nuclear magnetic resonance spectroscopy , molecule , circular dichroism , computational chemistry , organic chemistry , physics , quantum mechanics , astronomy
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 NH 2 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 . Chirality 28:215–225, 2016 . © 2016 Wiley Periodicals, Inc.