Pyridine-based strategies towards nitrogen isotope exchange and multiple isotope incorporation
Minghao Feng, Maylis Norlöff, Benoit Guichard, Steven Kealey, Timothée D’Anfray, P. Thuéry, Frédéric Taran, Antony D. Gee, Sophie Feuillastre, Davide Audisio
Abstract
Abstract Isotopic labeling is at the core of health and life science applications such as nuclear imaging, metabolomics and plays a central role in drug development. The rapid access to isotopically labeled organic molecules is a sine qua non condition to support these societally vital areas of research. Based on a rationally driven approach, this study presents an innovative solution to access labeled pyridines by a nitrogen isotope exchange reaction based on a Zincke activation strategy. The technology conceptualizes an opportunity in the field of isotope labeling. 15 N-labeling of pyridines and other relevant heterocycles such as pyrimidines and isoquinolines showcases on a large set of derivatives, including pharmaceuticals. Finally, we explore a nitrogen-to-carbon exchange strategy in order to access 13 C-labeled phenyl derivatives and deuterium labeling of mono-substituted benzene from pyridine- 2 H 5 . These results open alternative avenues for multiple isotope labeling on aromatic cores.