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Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy

[Image: see text] With renewed interest in atropisomerism of drug molecules, efficient methods to experimentally determine torsion rotational energy barriers are needed. Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in (19)F NMR...

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Autores principales: Kulyk, Svitlana, De Paul, Susan M., Marx, Matthew A., Peakman, Torren M., Smith, Christopher R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476184/
https://www.ncbi.nlm.nih.gov/pubmed/36120049
http://dx.doi.org/10.1021/acsomega.2c03316
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author Kulyk, Svitlana
De Paul, Susan M.
Marx, Matthew A.
Peakman, Torren M.
Smith, Christopher R.
author_facet Kulyk, Svitlana
De Paul, Susan M.
Marx, Matthew A.
Peakman, Torren M.
Smith, Christopher R.
author_sort Kulyk, Svitlana
collection PubMed
description [Image: see text] With renewed interest in atropisomerism of drug molecules, efficient methods to experimentally determine torsion rotational energy barriers are needed. Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in (19)F NMR and to use the data to study the kinetics of racemization and determine the rotational energy barrier of clinical compound MRTX1719. This method is complimentary to traditional chiral high-performance liquid chromatography (HPLC) and enhances the toolkit for chiral analysis techniques.
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spelling pubmed-94761842022-09-16 Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy Kulyk, Svitlana De Paul, Susan M. Marx, Matthew A. Peakman, Torren M. Smith, Christopher R. ACS Omega [Image: see text] With renewed interest in atropisomerism of drug molecules, efficient methods to experimentally determine torsion rotational energy barriers are needed. Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in (19)F NMR and to use the data to study the kinetics of racemization and determine the rotational energy barrier of clinical compound MRTX1719. This method is complimentary to traditional chiral high-performance liquid chromatography (HPLC) and enhances the toolkit for chiral analysis techniques. American Chemical Society 2022-08-31 /pmc/articles/PMC9476184/ /pubmed/36120049 http://dx.doi.org/10.1021/acsomega.2c03316 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Kulyk, Svitlana
De Paul, Susan M.
Marx, Matthew A.
Peakman, Torren M.
Smith, Christopher R.
Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy
title Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy
title_full Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy
title_fullStr Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy
title_full_unstemmed Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy
title_short Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted (19)F NMR Spectroscopy
title_sort atropisomeric racemization kinetics of mrtx1719 using chiral solvating agent-assisted (19)f nmr spectroscopy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476184/
https://www.ncbi.nlm.nih.gov/pubmed/36120049
http://dx.doi.org/10.1021/acsomega.2c03316
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