Main content area

Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands

Taylor, Nicholas J., Emer, Enrico, Preshlock, Sean, Schedler, Michael, Tredwell, Matthew, Verhoog, Stefan, Mercier, Joel, Genicot, Christophe, Gouverneur, Véronique
Journal of the American Chemical Society 2017 v.139 no.24 pp. 8267-8276
aromatic hydrocarbons, boron, drugs, esters, models, positron-emission tomography
Molecules labeled with fluorine-18 (¹⁸F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of ¹⁸F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated ¹⁸F-fluorination of aryl boron reagents with ¹⁸F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of ¹⁸F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.