The distribution, metabolism and ultimate fate of molecules within the body is central to the activity of pharmaceuticals. However, the introduction of radioisotopes into the metabolically stable carbon sites on drugs to probe these features typically requires toxic, radioactive gases such as [¹⁴C]CO and [¹⁴C]CO₂. Here we describe an approach to directly carbon-label carboxylic-acid-containing pharmaceuticals via a metal-catalysed functional group exchange reaction, forming ¹⁴C-labelled carboxylic-acid-containing drugs without radioactive gases, in one pot, using an easily available and handled carboxylic acid ¹⁴C source. To enable this process, a functional group metathesis of carbon–carbon covalent bonds in acid chloride functionalities is developed, exploiting the ability of nickel catalysts to both reversibly activate carbon–chloride bonds and exchange functionalities between organic molecules. The drug development applicability is illustrated by the direct incorporation of the ¹⁴C label or ¹³C label into an array of complex aryl, alkyl, vinyl and heterocyclic carboxylic acid drugs or drug candidates without gases or a special apparatus, at ambient conditions and without loss of the radiolabel.

体内分子的分布、代谢和最终命运是药物活性的核心。然而，将放射性同位素引入药物上代谢稳定的碳位点以探测这些特征通常需要有毒的放射性气体，例如[ ¹⁴ C]CO和[ ¹⁴ C]CO ₂。在这里，我们描述了一种通过金属催化的官能团交换反应直接碳标记含羧酸药物的方法，使用一种容易获得的方法在一锅中形成¹⁴ C标记的含羧酸药物，无需放射性气体。处理羧酸^14C源。为了实现这一过程，开发了酰基氯官能团中碳-碳共价键的官能团复分解，利用镍催化剂可逆地激活碳-氯键和有机分子之间交换官能团的能力。药物开发的适用性通过将¹⁴ C 标签或¹³ C 标签直接掺入一系列复杂的芳基、烷基、乙烯基和杂环羧酸药物或候选药物中来说明，无需气体或特殊设备，在环境条件下且无损失的放射性标记。