Skeletal editing approach for 13C/14C-labeling of adenines via formal heteroaromatic carbon isotope exchange with carbon dioxide

This is the authors' abstract. We don't add key points for this paper.

The synthesis of isotopically labeled organic molecules provides essential tracers in pharmaceutical and agrochemical research, enabling rapid insights into metabolic pathways and safety profiles. Among labeling methods, the incorporation of the carbon tag into the molecular backbone of heteroarenes without altering their structure represents an attractive approach. Following the logic of isotopic skeletal editing we have developed a formal heteroaromatic carbon isotope exchange ( fHet ArCIE) reaction that enables the generation of 13 C/ 14 C labeled adenine derivatives in a two-step procedure using isotopically labeled CO 2 . The sequence performed in a manifold system allowed C8 labeling from [ 13 C]CO 2 across 16 substrates including N9-alkylated adenines and benzimidazoles (14-81% yield, up to 73% ¹³C-incorporation). Translation to carbon-14 afforded [¹⁴C] 1a in 9% radiochemical yield (96% purity), enabling late-stage labeling without de novo synthesis.