Zhou Dong, Chu Wenhua, Chen Huaping, Xu Jinbin
Department of Radiology, School of Medicine, Washington University in Saint Louis, Saint Louis, Missouri 63110, United States.
ACS Med Chem Lett. 2023 Dec 18;15(1):116-122. doi: 10.1021/acsmedchemlett.3c00465. eCollection 2024 Jan 11.
Copper-mediated radiofluorination (CMRF) of organoboronic precursors is the method of choice for late-stage radiofluorination of aromatic compounds as positron emission tomography (PET) radiotracers. However, CMRF generally requires harsh reaction conditions, a large amount of substrates, and harsh solvents (e.g., DMA) to proceed, affording variable radiochemical yields (RCYs). Using [F]tosyl fluoride as the source of [F]fluoride, we have found a highly efficient CMRF of organoboronic precursors, assisted by a directing group (DG) at the position. The reaction can be carried out under mild conditions (even at room temperature) in acetonitrile and results in high RCYs, providing a novel strategy for the radiofluorination of aromatic compounds. The exploration of this strategy also provided more information about side reactions in CMRF. Using this strategy, [F]olaparib has been radiosynthesized in high RCYs, with high molar activity and high chemical and radiochemical purities, demonstrating the great potential of DG-assisted CMRF in the preparation of F-labeled PET radiotracers.
有机硼酸前体的铜介导放射性氟化（CMRF）是芳香族化合物作为正电子发射断层扫描（PET）放射性示踪剂进行后期放射性氟化的首选方法。然而，CMRF通常需要苛刻的反应条件、大量的底物以及苛刻的溶剂（如DMA）才能进行，导致放射性化学产率（RCY）各不相同。使用对甲苯磺酰氟作为氟化物源，我们发现了一种高效的有机硼酸前体CMRF方法，该方法由邻位的导向基团（DG）辅助。该反应可以在温和条件下（甚至在室温下）于乙腈中进行，并产生高RCY，为芳香族化合物的放射性氟化提供了一种新策略。对该策略的探索还提供了更多关于CMRF中副反应的信息。使用该策略，已以高RCY、高摩尔活性以及高化学和放射性化学纯度放射合成了氟代奥拉帕利，证明了DG辅助CMRF在制备F标记PET放射性示踪剂方面的巨大潜力。
