Late-Stage Copper-Catalyzed Radiofluorination of an Arylboronic Ester Derivative of Atorvastatin
Late-Stage Copper-Catalyzed Radiofluorination of an Arylboronic Ester Derivative of Atorvastatin
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DOI：
10.3390/molecules24234210
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发表时间：
2019-12-01
期刊：
影响因子：
4.6
通讯作者：
Elsinga, Philip H.
中科院分区：
文献类型：
--
作者：
Clemente, Goncalo S.;Zarganes-Tzitzikas, Tryfon;Elsinga, Philip H.
对于后期F-18-β-内酰胺策略存在未满足的需求，以标记具有广泛的药物化学相关官能团的分子，特别是（杂）芳烃，旨在使用正电子发射断层扫描（PET）获得关于药代动力学/药效学（PK/PD）的独特体内信息。在过去的几年中，铜介导的氧化放射性芳基硼酸酯/酸出现，并已成功地在小分子含有相对简单的（杂）芳香族基团。然而，这种技术很少用于放射合成临床上重要的分子，含有更复杂的骨架与几个芳香基序。在这项工作中，我们增加了一个新的条目，这个非常有限的数据库，提出我们最近的结果对F-18-阿托伐他汀的芳基硼酸酯衍生物。[F-18]F-的中等平均转化率（12%）与类似复杂分子的报告一致，强调通过文献进行概述，以了解放射性标记变量和限制，从而防止持续提高产率。尽管如此，目前所报告的程序差异仍然妨碍了协商一致的结论性产出。
There is an unmet need for late-stage F-18-fluorination strategies to label molecules with a wide range of relevant functionalities to medicinal chemistry, in particular (hetero)arenes, aiming to obtain unique in vivo information on the pharmacokinetics/pharmacodynamics (PK/PD) using positron emission tomography (PET). In the last few years, Cu-mediated oxidative radiofluorination of arylboronic esters/acids arose and has been successful in small molecules containing relatively simple (hetero)aromatic groups. However, this technique is sparsely used in the radiosynthesis of clinically significant molecules containing more complex backbones with several aromatic motifs. In this work, we add a new entry to this very limited database by presenting our recent results on the F-18-fluorination of an arylboronic ester derivative of atorvastatin. The moderate average conversion of [F-18]F- (12%), in line with what has been reported for similarly complex molecules, stressed an overview through the literature to understand the radiolabeling variables and limitations preventing consistently higher yields. Nevertheless, the current disparity of procedures reported still hampers a consensual and conclusive output.