One-Pot Formal Carboradiofluorination of Alkenes: A Toolkit for Positron Emission Tomography Imaging Probe Development.
One-Pot Formal Carboradiofluorination of Alkenes: A Toolkit for Positron Emission Tomography Imaging Probe Development.
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DOI：
10.1021/jacs.3c04548
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发表时间：
2023-08
影响因子：
15
通讯作者：
Mónica Rivas;Sashi Debnath;S. Giri;Yusuf M Noffel;Xiankai Sun;V. Gevorgyan
中科院分区：
文献类型：
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作者：
Mónica Rivas;Sashi Debnath;S. Giri;Yusuf M Noffel;Xiankai Sun;V. Gevorgyan
我们报道了第一个用易接近的烯烃作为假体前体和偶联伙伴的一锅正构烷烃碳放射性氟化反应。该方法的特点是快速顺序马可夫尼科夫选择性碘氟化和光诱导Pd（0/I/II）催化烷基Heck反应，作为一种温和而稳健的氟-18 （18F）放射化学方法，用于正电子发射断层扫描（PET）成像探针的开发。以碘氟化中间体的形式分离出一类用于PET成像探针合成的新型假体基团，收率中等至优异。进行了一锅形式烯基氟化反应，产生了30多种生物活性分子的类似物。Pd（0/I/II）歧管在PET探针开发中的进一步应用通过富电子烯烃的直接碳（无线电）氟化说明。该方法已成功地转化为放射性标签的范围广泛的医学相关的小分子在一般良好的放射化学转化。该方案进一步优化，以适应无载体添加的条件，具有相似的效率，为未来（预）临床翻译。此外，在放射化学模块中，假肢基团的放射合成是自动化的，以促进其在多步放射化学反应中的实际应用。
We report the first one-pot formal alkene carboradiofluorination reaction employing easily accessible alkenes as both prosthetic group precursors and coupling partners. The methodology features rapid sequential Markovnikov-selective iodofluorination and photoinduced Pd(0/I/II)-catalyzed alkyl Heck reaction as a mild and robust fluorine-18 (18F) radiochemical approach for positron emission tomography (PET) imaging probe development. A new class of prosthetic groups for PET imaging probe synthesis was isolated as iodofluorinated intermediates in moderate to excellent yields. The one-pot formal alkenylfluorination reaction was carried out to produce over 30 analogues of a wide range of bioactive molecules. Further application of the Pd(0/I/II) manifold in PET probe development was illustrated by the direct carbo(radio)fluorination of electron-rich alkenes. The methods were successfully translated to radiolabel a broad scope of medicinally relevant small molecules in generally good radiochemical conversion. The protocol was further optimized to accommodate no-carrier-added conditions with similar efficiency for future (pre)clinical translation. Moreover, the radiosynthesis of prosthetic groups was automated in a radiochemistry module to facilitate its practical use in multistep radiochemical reactions.