Direct Carbon Isotope Exchange through Decarboxylative Carboxylation

Cian Kingston; Michael A Wallace; Alban J Allentoff; Justine N deGruyter; Jason S Chen; Sharon X Gong; Samuel Bonacorsi Jr; Phil S Baran

doi:10.1021/jacs.8b12035

Direct Carbon Isotope Exchange through Decarboxylative Carboxylation

J Am Chem Soc. 2019 Jan 16;141(2):774-779. doi: 10.1021/jacs.8b12035. Epub 2019 Jan 3.

Authors

Cian Kingston¹, Michael A Wallace², Alban J Allentoff², Justine N deGruyter¹, Jason S Chen³, Sharon X Gong², Samuel Bonacorsi Jr², Phil S Baran¹

Affiliations

¹ Department of Chemistry , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States.
² Radiochemistry , Bristol-Myers Squibb Company , P.O. Box 4000, Princeton , New Jersey 08543 , United States.
³ Automated Synthesis Facility , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States.

Abstract

A two-step degradation-reconstruction approach to the carbon-14 radiolabeling of alkyl carboxylic acids is presented. Simple activation via redox-active ester formation was followed by nickel-mediated decarboxylative carboxylation to afford a range of complex compounds with ample isotopic incorporations for drug metabolism and pharmacokinetic studies. The practicality and operational simplicity of the protocol were demonstrated by its use in an industrial carbon-14 radiolabeling setting.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Carbon Isotopes / chemistry
Carbon Radioisotopes / chemistry
Carboxylic Acids / chemical synthesis
Carboxylic Acids / chemistry*
Catalysis
Decarboxylation
Isotope Labeling / methods
Nickel / chemistry
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / chemistry*

Substances

Carbon Isotopes
Carbon Radioisotopes
Carboxylic Acids
Radiopharmaceuticals
Nickel
Carbon-14
Carbon-13

Grants and funding

R35 GM118176/GM/NIGMS NIH HHS/United States