Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds

Yong Yao Loh, Kazunori Nagao, Andrew J. Hoover, David Hesk, Nelo R. Rivera, Steven L. Colletti, Ian W. Davies, David W.C. MacMillan

Research output: Contribution to journalArticlepeer-review

352 Scopus citations


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 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.

Original languageEnglish (US)
Pages (from-to)1182-1187
Number of pages6
Issue number6367
StatePublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • General


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