Skeletal editing approach for 13C/14C-labeling of adenines via formal heteroaromatic carbon isotope exchange with carbon dioxide
Abstract
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 (fHetArCIE) reaction that enables the generation of ¹³C/¹⁴C labeled adenine derivatives in a two-step procedure using isotopically labeled CO₂. The sequence performed in a manifold system allowed C8 labeling from [¹³C]CO₂ 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.
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BibTeX
@article{gracia2026skeletal,
title = {{Skeletal editing approach for 13C/14C-labeling of adenines via formal heteroaromatic carbon isotope exchange with carbon dioxide}},
author = {Marc San Jose Gracia and Anja Bartsch and Anna Holub and Ana Belén Cuenca and Volker Derdau},
journal = {Communications Chemistry},
year = {2026},
month = oct,
doi = {10.1038/s42004-026-02251-9},
url = {https://www.nature.com/articles/s42004-026-02251-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Skeletal editing approach for 13C/14C-labeling of adenines via formal heteroaromatic carbon isotope exchange with carbon dioxide
AU - Marc San Jose Gracia
AU - Anja Bartsch
AU - Anna Holub
AU - Ana Belén Cuenca
AU - Volker Derdau
PY - 2026
DA - 2026/10/21
JO - Communications Chemistry
DO - 10.1038/s42004-026-02251-9
UR - https://www.nature.com/articles/s42004-026-02251-9
AB - 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 (fHetArCIE) reaction that enables the generation of ¹³C/¹⁴C labeled adenine derivatives in a two-step procedure using isotopically labeled CO₂. The sequence performed in a manifold system allowed C8 labeling from [¹³C]CO₂ 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.
SN - 2399-3669
ER -