title: Stereochemistry of the tadalafil diastereoisomers: a critical assessment of vibrational circular dichroism, electronic circular dichroism, and optical rotatory dispersion.
abstract: The stereochemistry of all four stereoisomers of tadalafil is determined using vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotatory dispersion (ORD) spectroscopy. By comparing experimentally obtained VCD spectra to computationally simulated ones, the absolute configuration of the enantiomeric pair (6R, 12aR)/(6S, 12aS) can be confidently assigned without prior knowledge of their relative stereochemistry. IR and NMR spectra are used to aid the assignment of the relative stereochemistry. The IR and VCD difference spectra further confirm the assignment of all stereoisomers. ECD and ORD spectra are used to investigate the complementarity of the three chiroptical techniques. VCD spectroscopy itself is found to have the ability to identify diastereoisomers, and simultaneous use of these chiroptical spectroscopic methods and NMR chemical shifts aids in increasing the reliability of stereochemistry assignment of diastereoisomers.
authors.affiliation: Department of Chemistry, ‡European Centre for Chirality, EC2, University of Antwerp , Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Shi
authors.initials: S
authors.lastname: Qiu
authors.forename: Ewoud
authors.initials: E
authors.lastname: De Gussem
authors.forename: Kourosch Abbaspour
authors.initials: KA
authors.lastname: Tehrani
authors.forename: Sergey
authors.initials: S
authors.lastname: Sergeyev
authors.forename: Patrick
authors.initials: P
authors.lastname: Bultinck
authors.forename: Wouter
authors.initials: W
authors.lastname: Herrebout
mesh_terms: D002243:Carbolines / Q000737:chemistry*; D002942:Circular Dichroism; D008968:Molecular Conformation; D009905:Optical Rotatory Dispersion; D011789:Quantum Theory; D013237:Stereoisomerism; D000068581:Tadalafil; D014732:Vibration
chemical_list: D002243:Carbolines; D000068581:Tadalafil