Photoredox-Mediated Hydrogen Isotope Exchange Reactions of Amino-Acids,Peptides, and Peptide-Derived Drugs |
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Authors: | Dr. Fabien Legros Dr. Patricia Fernandez-Rodriguez Dr. Anurag Mishra Remo Weck Dr. Armin Bauer Dr. Martin Sandvoss Dr. Sven Ruf Dr. María Méndez Dr. Helena Mora-Radó Dr. Nils Rackelmann Dr. Christoph Pöverlein Dr. Volker Derdau |
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Affiliation: | 1. Integrated Drug Discovery, Sanofi-Aventis (Deutschland) GmbH, Industriepark Höchst, 65926 Frankfurt, Germany;2. TIDES, Sanofi-Aventis (Deutschland) GmbH, Industriepark Höchst, 65926 Frankfurt, Germany |
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Abstract: | Hydrogen isotopically labelled compounds are essential diagnostic tools in drug research and development, as they provide vital information about the biological metabolism of drug candidates and their metabolites. Herein we report a photoredox-initiated hydrogen atom transfer (HAT) protocol which efficiently and selectively introduces deuterium or tritium at C(sp3)−H bonds, utilizing heavy water (D2O or T2O) as the hydrogen isotope source, and a guanidine base. This protocol has been successfully applied to the incorporation of deuterium in several amino acids (lysine, glycine and proline) and small peptides. Finally, the method has been applied to tritium, because tritium-labelled peptides are essential for application in biological experiments, such as ligand-binding assays, or absorption, distribution, metabolism, and excretion (ADME) studies. |
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Keywords: | amino acids C−H activation hydrogen isotope exchange peptide drugs photocatalysis |
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