Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
Science for Life Laboratory, Department of Medicinal Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
Molecules. 2017 Oct 10;22(10):1688. doi: 10.3390/molecules22101688.
Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [C]carbon monoxide. Starting with amines and [C]carbon monoxide, both symmetrical and unsymmetrical C-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [C]carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/μmol-319 GBq/μmol). DFT calculations were found to support a reaction mechanism proceeding through an C-labelled isocyanate intermediate.
正电子发射断层扫描是一种成像技术，在临床环境和基础研究中都有应用，用于研究生物过程。研究中使用了一种正电子发射放射性同位素（如碳-11）掺入的生物活性分子作为 PET 示踪剂。因此，开发将放射性同位素掺入的稳健方法至关重要。尿素官能团存在于许多生物活性化合物中，因此是用 [C]一氧化碳的形式掺入碳-11 的有吸引力的目标。从胺和 [C]一氧化碳开始，通过钯（II）介导的氧化羰基化合成了对称和不对称的 C 标记的尿素，在衰变校正的放射化学产率高达 65%。通过对可溶性环氧化物水解酶抑制剂的摩尔活性（247GBq/μmol-319GBq/μmol），显示了使用 [C]一氧化碳的附加优势。DFT 计算被发现支持通过 C 标记的异氰酸酯中间体进行的反应机制。
