Journal
SCIENCE
Volume 358, Issue 6367, Pages 1182-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aap9674
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Funding
- National Institutes of Health (NIH) [R01 GM103558-04]
- Agency for Science, Technology and Research (A*STAR)
- Japan Society for the Promotion of Science
- Merck
- Abbvie
- BMS
- Janssen
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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 a-amino sp(3) 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 T-2, 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.
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