Electrochemical fluorodecarboxylation for the labelling of gem-difluoro(cyclo)alkanes/amines

用于标记偕二氟（环）烷烃/胺的电化学氟脱羧

• 批准号: EP/X02458X/1
• 负责人: Long Yang
• 金额: $ 26万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX02458X%2F1
• 关键词: Electrochemical; fluorodecarboxylation; labelling; gem; difluoro

Positron emission tomography (PET) is a powerful molecular imaging modality for diagnosis, monitoring disease progression, studying biological processes in vivo, and investigating the efficacy of drugs. Among the radioisotopes employed for the preparation of PET probes, fluorine-18 is a widely used and clinically relevant radionuclide in part due to its favourable decay properties, and the numerous clinical applications. While radiochemists have in recent years focused their efforts on methods enabling 18F-labelled fluorination and trifluoromethylation of (hetero)arenes, 18F-radiolabelled gem-difluorinated reactions have been much less studied despite the importance of the gem-difluoromethylene group (CF2) in radioligand design for drug discovery programmes. Herein, we propose a solution merging electrochemistry and 18F radiochemistry with the development of a novel electrochemical fluorodecarboxylation process affording 18F-labelled gem-difluoro(cyclo)alkanes and (cyclo)amines including structurally complex pharmaceutical drugs.

正电子发射断层扫描（PET）是一种功能强大的分子成像模式，用于诊断，监测疾病进展，研究体内生物过程，并研究药物的疗效。在用于制备PET探针的放射性同位素中，氟-18是一种广泛使用的和临床相关的放射性核素，部分原因是其有利的衰变性质和众多的临床应用。虽然放射化学家近年来将他们的努力集中在使18F-标记的双（三氟甲基化）芳烃和三氟甲基化的方法上，但18F-放射性标记的偕-二氟化反应的研究要少得多，尽管偕-二氟亚甲基（CF 2）在药物发现计划的放射性配体设计中的重要性。在此，我们提出了一种解决方案，合并电化学和18F放射化学与一种新的电化学氟脱羧过程的发展，提供18F-标记的偕二氟（环）烷烃和（环）胺，包括结构复杂的药物。