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

ABSTRACT: 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 ¹⁹F 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.

SUBMITTER: Kulyk S

PROVIDER: S-EPMC9476184 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Kulyk Svitlana S De Paul Susan M SM Marx Matthew A MA Peakman Torren M TM Smith Christopher R CR

ACS omega 20220831 36

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 19F 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 l ...[more]

PMID: 36120049

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