Ford Joseph, Ortalli Sebastiano, Gouverneur Véronique
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom.
Angew Chem Int Ed Engl. 2024 Jun 21;63(26):e202404957. doi: 10.1002/anie.202404957. Epub 2024 May 15.
The difluoromethyl functionality has proven useful in drug discovery, as it can modulate the properties of bioactive molecules. For PET imaging, this structural motif has been largely underexploited in (pre)clinical radiotracers due to a lack of user-friendly radiosynthetic routes. This Minireview provides an overview of the challenges facing radiochemists and summarises the efforts made to date to access F-difluoromethyl-containing radiotracers. Two distinct approaches have prevailed, the first of which relies on F-fluorination. A second approach consists of a F-difluoromethylation process, which uses F-labelled reagents capable of releasing key reactive intermediates such as the [F]CFH radical or [F]difluorocarbene. Finally, we provide an outlook for future directions in the radiosynthesis of [F]CFH compounds and their application in tracer radiosynthesis.
二氟甲基官能团已被证明在药物发现中很有用，因为它可以调节生物活性分子的性质。对于正电子发射断层扫描（PET）成像，由于缺乏用户友好的放射性合成路线，这种结构基序在（临床前）放射性示踪剂中基本上未得到充分利用。本综述概述了放射化学家面临的挑战，并总结了迄今为止为获得含F-二氟甲基的放射性示踪剂所做的努力。有两种不同的方法占主导地位，第一种方法依赖于F-氟化。第二种方法包括F-二氟甲基化过程，该过程使用能够释放关键反应中间体（如[F]CFH自由基或[F]二氟卡宾）的F标记试剂。最后，我们展望了[F]CFH化合物放射性合成的未来方向及其在示踪剂放射性合成中的应用。
