Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics
Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics
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DOI：
10.1038/ncomms5365
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发表时间：
2014-07-01
影响因子：
16.6
通讯作者：
Liang, Steven H.
中科院分区：
文献类型：
--
作者：
Rotstein, Benjamin H.;Stephenson, Nickeisha A.;Liang, Steven H.
~(18)F(t(1/2)=109.7分钟)是用于正电子发射断层扫描分子成像的最常用的放射性核素。在合成高比活度放射性示踪剂时，通常会进行适当活化(缺电子)芳香底物与无载体[F-18]氟离子的亲核芳香取代反应。尽管为非活化芳烃开发一种通用的F-18标记技术作出了广泛的努力，但实现这一目标的迫切和未得到满足的需求。在这里，我们描述了一种有效的解决方案，它依赖于螺环高价碘(III)络合物的化学，这些络合物作为快速、一步区域选择性地与[F-18]氟化物进行放射性氟化的前体。这一方法被证明是一种有效的放射性标记方法，用于标记各种非活化的官能化芳烃和杂芳烃，包括带有给电子基的芳烃底物、大体积的邻位官能团、苄基取代基和间位取代的吸电子基团。合成了多功能分子和一系列以前难以捉摸的F-18标记的积木、化合物和放射性药物。
Fluorine-18 (t(1/2)=109.7 min) is the most commonly used isotope to prepare radiopharmaceuticals for molecular imaging by positron emission tomography (PET). Nucleophilic aromatic substitution reactions of suitably activated (electron-deficient) aromatic substrates with no-carrier-added [F-18] fluoride ion are routinely carried out in the synthesis of radiotracers in high specific activities. Despite extensive efforts to develop a general F-18-labelling technique for non-activated arenes there is an urgent and unmet need to achieve this goal. Here we describe an effective solution that relies on the chemistry of spirocyclic hypervalent iodine(III) complexes, which serve as precursors for rapid, one-step regioselective radiofluorination with [F-18] fluoride. This methodology proves to be efficient for radiolabelling a diverse range of non-activated functionalized arenes and heteroarenes, including arene substrates bearing electron-donating groups, bulky ortho functionalities, benzylic substituents and meta-substituted electron-withdrawing groups. Polyfunctional molecules and a range of previously elusive F-18-labelled building blocks, compounds and radio-pharmaceuticals are synthesized.