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- Title
The Role of the Transient Atropisomerism and Chirality of Flurbiprofen Unveiled by Laser‐Ablation Rotational Spectroscopy.
- Authors
Verde, Andrés; López, Juan Carlos; Blanco, Susana
- Abstract
The combination of atropisomerism and chirality in flurbiprofen is shown to be relevant concerning its pharmacological activity. The two most stable conformers of a total of eight theoretically predicted for each R‐ or S‐ flurbiprofen enantiomers have been isolated in the cooling conditions of a supersonic jet and structurally characterized by laser ablation Fourier transform microwave spectroscopy. The detected conformers, whose structure is mainly defined by three dihedral angles, only differ in the sign of the phenyl torsion angle giving rise to Sa and Ra atropisomers. A comparison with the structures available for the R‐ and S‐ enantiomers complexed to COX isoforms reveals that the enzymes select only the Sa atropisomers, resulting in a diastereoisomer‐specific recognition. The most stable gas phase conformer is exclusively selected when using the S‐ enantiomer while the second is recognized only for the R‐ enantiomer. These experimental results highlight the importance of atropisomerism in drug design.
- Subjects
MICROWAVE spectroscopy; FOURIER transform spectroscopy; CHIRALITY; FLURBIPROFEN; DIHEDRAL angles; LASER ablation
- Publication
Chemistry - A European Journal, 2023, Vol 29, Issue 25, p1
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.202300064