氚
化学
氘
背景(考古学)
催化作用
组合化学
配体(生物化学)
放射化学
有机化学
生物化学
量子力学
生物
物理
古生物学
受体
核物理学
作者
Yong Yao Loh,Kazunori Nagao,Andrew J. Hoover,David Hesk,Nelo R. Rivera,Steven L. Colletti,Ian W. Davies,David W. C. MacMillan
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2017-12-01
卷期号:358 (6367): 1182-1187
被引量:387
标识
DOI:10.1126/science.aap9674
摘要
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.
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