Direct carbon isotope exchange of pharmaceuticals via reversible decyanation

Minghao Feng (1) , Joao de Oliveira (1) , Antoine Sallustrau (1) , Gianluca Destro (1) , Pierre Thuéry (2) , Sebastien Roy (3) , Thibault Cantat (2) , Charles Elmore (3) , Jorg Blankenstein (3) , Frédéric Taran (1) , Davide Audisio (1)

1 SCBM - Service de Chimie Bio-Organique et de Marquage
2 LCMCE - Laboratoire de Chimie Moléculaire et de Catalyse pour l'Energie (ex LCCEF)
3 Sanofi R & D, Integrated Drug Discovery, In Vitro Biology & Pharmacology

The incorporation of carbon-14 allows tracking of organic molecules and provides vital knowledge on their fate. This information is critical in pharmaceutical development, crop science, and human food safety evaluation. Herein, a transition-metal-catalyzed procedure enabling carbon isotope exchange on aromatic nitriles is described. By utilizing the radiolabeled precursor Zn([14C]CN)2, this protocol allows the insertion of the desired carbon tag without the need for structural modifications, in a single step. By reducing synthetic costs and limiting the generation of radioactive waste, this procedure will facilitate the labeling of nitrile containing drugs and accelerate 14C-based ADME studies supporting drug development.

Domains: Medicinal Chemistry; Organic chemistry

Minghao Feng, Joao de Oliveira, Antoine Sallustrau, Gianluca Destro, Pierre Thuéry, et al.. Direct carbon isotope exchange of pharmaceuticals via reversible decyanation. Journal of the American Chemical Society, 2021, 143 (15), pp.5659-5665. ⟨10.1021/jacs.1c01923⟩. ⟨cea-03204990⟩