Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds
Top Cited Papers
- 1 December 2017
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 358 (6367), 1182-1187
- https://doi.org/10.1126/science.aap9674
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 α-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.Keywords
Funding Information
- National Institutes of Health (award351006, R01 GM103558-04)
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