The Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University , Gustav Wieds Vej 14, 8000 Aarhus, Denmark.
J Am Chem Soc. 2015 Feb 4;137(4):1548-55. doi: 10.1021/ja511441u. Epub 2015 Jan 26.
We describe the successful implementation of palladium-aryl oxidative addition complexes as stoichiometric reagents in carbonylation reactions with (11)CO to produce structurally challenging, pharmaceutically relevant compounds. This method enables the first (11)C-carbonyl labeling of an approved PET tracer, [(11)C]raclopride, for the dopamine D2/D3 receptor by carbonylation with excellent radiochemical purity and yield. Two other molecules, [(11)C]olaparib and [(11)C]JNJ 31020028, were efficiently labeled in this manner. The technique distinguishes itself from existing methods by the markedly improved purity profiles of the tracer molecules produced and provides access to complex structures in synthetically useful yields, hereby offering a viable alternative to other (11)C-labeling strategies.
我们描述了钯-芳基氧化加成配合物作为(11)CO 羰基化反应的化学计量试剂的成功应用,以生产具有挑战性的结构、具有药物相关性的化合物。这种方法使首个批准的 PET 示踪剂[(11)C]raclopride 通过羰基化反应以优异的放射化学纯度和产率进行(11)C-羰基标记成为可能。另外两种分子[(11)C]olaparib 和[(11)C]JNJ 31020028 也以这种方式得到了有效标记。该技术通过显著提高所产生示踪剂分子的纯度曲线与现有的方法区分开来,并以合成上有用的产率提供了对复杂结构的访问,从而为其他(11)C-标记策略提供了可行的替代方案。