Ruthenium(II)-Catalyzed Hydrogen Isotope Exchange of Pharmaceutical Drugs by C-H Deuteration and C-H Tritiation
Ruthenium(II)-Catalyzed Hydrogen Isotope Exchange of Pharmaceutical Drugs by C-H Deuteration and C-H Tritiation
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DOI：
10.1002/cctc.201902051
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发表时间：
2019-12-05
期刊：
影响因子：
4.5
通讯作者：
Ackermann, Lutz
中科院分区：
文献类型：
--
作者：
Mueller, Valentin;Weck, Remo;Ackermann, Lutz
定义良好的双羧酸钌配合物能够与弱配位、合成有用的羧酸进行选择性的正氘化，并具有出色的同位素标记水平。催化系统的强大性质反映在操作简单的方式下具有广泛的官能团耐受性，允许对具有挑战性的药物和生物活性杂环基序进行同位素标记。我们的方法的合成能力是通过选择性的氚标记瑞格列奈，一种抗糖尿病药物，提供了明确的氚标记疗法。
Well-defined ruthenium(II) biscarboxylate complexes enabled selective ortho-deuteration with weakly-coordinating, synthetically useful carboxylic acid with outstanding levels of isotopic labeling. The robust nature of the catalytic system was reflected by a broad functional group tolerance in an operationally-simple manner, allowing the isotope labeling of challenging pharmaceuticals and bioactive heterocyclic motifs. The synthetic power of our method was highlighted by the selective tritium-labeling of repaglinide, an antidiabetic drug, providing access to defined tritium labeled therapeutics.