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Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds.

ABSTRACT: Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research, providing vital information about the biological fate of drugs and drug metabolites. Herein we demonstrate that a photoredox-mediated hydrogen atom transfer protocol can efficiently and selectively install deuterium (D) and tritium (T) at ?-amino sp3 carbon-hydrogen bonds in a single step, using isotopically labeled water (D2O or T2O) as the source of hydrogen isotope. In this context, we also report a convenient synthesis of T2O from T2, providing access to high-specific-activity T2O. This protocol has been successfully applied to the high incorporation of deuterium and tritium in 18 drug molecules, which meet the requirements for use in ligand-binding assays and absorption, distribution, metabolism, and excretion studies.

SUBMITTER: Loh YY

PROVIDER: S-EPMC5907472 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds.

Loh Yong Yao YY Nagao Kazunori K Hoover Andrew J AJ Hesk David D Rivera Nelo R NR Colletti Steven L SL Davies Ian W IW MacMillan David W C DWC

Science (New York, N.Y.) 20171109 6367

Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research, providing vital information about the biological fate of drugs and drug metabolites. Herein we demonstrate that a photoredox-mediated hydrogen atom transfer protocol can efficiently and selectively install deuterium (D) and tritium (T) at α-amino sp3 carbon-hydrogen bonds in a single step, using isotopically labeled water (D2O or T2O) as the source of ...[more]

PMID: 29123019

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