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Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds

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Science  09 Nov 2017:
eaap9674
DOI: 10.1126/science.aap9674

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Abstract

Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in pharmaceutical 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 (HAT) protocol can efficiently and selectively install deuterium and tritium at α-amino sp3 C–H 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 (ADME) studies.

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