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Catalytic Deuterium Incorporation within Metabolically Stable ?-Amino C-H Bonds of Drug Molecules.

ABSTRACT: An efficient deuteration process of ?-amino C-H bonds in various N-alkylamine-based pharmaceutical compounds has been developed. Catalytic reactions begin with the action of Lewis acidic B(C6F5)3 and Brønsted basic N-alkylamine, converting a drug molecule into the corresponding enamine. The acid/base catalysts also promote the dedeuteration of acetone-d6 to afford a deuterated ammonium ion. Ensuing deuteration of the enamine then leads to the formation of ?-deuterated bioactive amines with up to 99% deuterium incorporation.

SUBMITTER: Chang Y

PROVIDER: S-EPMC7123439 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Catalytic Deuterium Incorporation within Metabolically Stable β-Amino C-H Bonds of Drug Molecules.

Chang Yejin Y Yesilcimen Ahmet A Cao Min M Zhang Yuyang Y Zhang Bochao B Chan Jessica Z JZ Wasa Masayuki M

Journal of the American Chemical Society 20190909 37

An efficient deuteration process of β-amino C-H bonds in various N-alkylamine-based pharmaceutical compounds has been developed. Catalytic reactions begin with the action of Lewis acidic B(C6F5)3 and Brønsted basic N-alkylamine, converting a drug molecule into the corresponding enamine. The acid/base catalysts also promote the dedeuteration of acetone-d6 to afford a deuterated ammonium ion. Ensuing deuteration of the enamine then l ...[more]

PMID: 31480842

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