Title
Stereochemistry of the tadalafil diastereoisomers : a critical assessment of vibrational circular dichroism, electronic circular dichroism, and optical rotatory dispersion
Author
Faculty/Department
Faculty of Sciences. Chemistry
Publication type
article
Publication
Washington, D.C. ,
Subject
Chemistry
Pharmacology. Therapy
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Volume/pages
56(2013) :21 , p. 8903-8914
ISSN
0022-2623
ISI
000327111100054
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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.
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