TY - JOUR
T1 - Exploration of Directing-Group-Assisted, Copper-Mediated Radiofluorination and Radiosynthesis of [18F]Olaparib
AU - Zhou, Dong
AU - Chu, Wenhua
AU - Chen, Huaping
AU - Xu, Jinbin
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2024/1/11
Y1 - 2024/1/11
N2 - 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 [18F]tosyl fluoride as the source of [18F]fluoride, we have found a highly efficient CMRF of organoboronic precursors, assisted by a directing group (DG) at the ortho 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, [18F]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 18F-labeled PET radiotracers.
AB - 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 [18F]tosyl fluoride as the source of [18F]fluoride, we have found a highly efficient CMRF of organoboronic precursors, assisted by a directing group (DG) at the ortho 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, [18F]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 18F-labeled PET radiotracers.
KW - [F]olaparib
KW - copper-mediated radiofluorination
KW - directing group
KW - fluorine-18
KW - poly[ADP-ribose] polymerase 1
KW - positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=85181073016&partnerID=8YFLogxK
U2 - 10.1021/acsmedchemlett.3c00465
DO - 10.1021/acsmedchemlett.3c00465
M3 - Article
C2 - 38229754
AN - SCOPUS:85181073016
SN - 1948-5875
VL - 15
SP - 116
EP - 122
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
IS - 1
ER -