Efficient palladium-catalyzed electrocarboxylation enables late-stage carbon isotope labelling

Gabriel M. F. Batista, Ruth Ebenbauer, Craig Day, Jonas Bergare, Karoline T. Neumann, Kathrin H. Hopmann, Charles S. Elmore, Alonso Rosas-Hernández () and Troels Skrydstrup ()
Additional contact information
Gabriel M. F. Batista: Aarhus University
Ruth Ebenbauer: Aarhus University
Craig Day: Aarhus University
Jonas Bergare: Pharmaceutical Sciences R&D AstraZeneca
Karoline T. Neumann: Aarhus University
Kathrin H. Hopmann: UiT—The Arctic University of Norway
Charles S. Elmore: Pharmaceutical Sciences R&D AstraZeneca
Alonso Rosas-Hernández: Aarhus University
Troels Skrydstrup: Aarhus University

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: Abstract Carbon isotope labelling of bioactive molecules is essential for accessing the pharmacokinetic and pharmacodynamic properties of new drug entities. Aryl carboxylic acids represent an important class of structural motifs ubiquitous in pharmaceutically active molecules and are ideal targets for the installation of a radioactive tag employing isotopically labelled CO2. However, direct isotope incorporation via the reported catalytic reductive carboxylation (CRC) of aryl electrophiles relies on excess CO2, which is incompatible with carbon-14 isotope incorporation. Furthermore, the application of some CRC reactions for late-stage carboxylation is limited because of the low tolerance of molecular complexity by the catalysts. Herein, we report the development of a practical and affordable Pd-catalysed electrocarboxylation setup. This approach enables the use of near-stoichiometric 14CO2 generated from the primary carbon-14 source Ba14CO3, facilitating late-stage and single-step carbon-14 labelling of pharmaceuticals and representative precursors. The proposed isotope-labelling protocol holds significant promise for immediate impact on drug development programmes.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46820-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46820-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-46820-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().