Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate.
Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate.
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DOI：
10.1016/j.apradiso.2014.06.013
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Sadeghi S
中科院分区：
文献类型：
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作者：
He Q;Wang Y;Alfeazi I;Sadeghi S
本文提出了一种通过阳离子中间体直接亲核氟化来实现芳香分子18f氟化的电化学方法。该反应在遥控自动平台上进行。叔丁基氧羰基（Boc）保护的儿茶酚是正电子发射断层扫描（PET）探针的中间模型分子（3,4-二羟基-6-[18F]氟-l-苯丙氨酸）的亲核电化学氟化。在含有Et3N·3HF和其他配套电解质的乙腈中，在恒电位阳极氧化下实现氟化。影响放射性氟化效率的因素包括前驱体浓度、Et3N·3HF浓度、支撑电解质类型、温度和时间以及施加电位。在Et3N·3HF （0.033 M）和NBu4PF6 （0.05 M）的乙腈溶液中电解0.1 M的4-叔丁基-二boc-儿茶酚1 h后，获得了10.4±0.6% （n = 4）的放射性氟化效率和43 GBq/mmol的比活性。采用密度泛函理论（DFT）解释了叔丁基官能团对电化学氧化和随后氟化的促进作用。
An electrochemical method with the ability to conduct 18F-fluorination of aromatic molecules through direct nucleophilic fluorination of cationic intermediates is presented in this paper. The reaction was performed on a remote-controlled automatic platform. Nucleophilic electrochemical fluorination of tert-butyloxycarbonyl (Boc) protected catechol, an intermediate model molecule for the positron emission tomography (PET) probe (3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine), was performed. Fluorination was achieved under potentiostatic anodic oxidation in acetonitrile containing Et3N · 3HF and other supporting electrolytes. Radiofluorination efficiency was influenced by a number of variables, including the concentration of the precursor, concentration of Et3N · 3HF, type of supporting electrolyte, temperature and time, as well as applied potentials. Radiofluorination efficiency of 10.4 ± 0.6% (n = 4) and specific activity of up to 43 GBq/mmol was obtained after 1 h electrolysis of 0.1 M of 4-tert-butyl-diboc-catechol in the acetonitrile solution of Et3N · 3HF (0.033 M) and NBu4PF6 (0.05 M). Density functional theory (DFT) was employed to explain the tert-butyl functional group facilitation of electrochemical oxidation and subsequent fluorination.