nhibition of radical reactions for an improved potassium tert-butoxide-promoted 11C-methylation strategy for the synthesis of α-11C-methyl amino acids
nhibition of radical reactions for an improved potassium tert-butoxide-promoted 11C-methylation strategy for the synthesis of α-11C-methyl amino acids
复制标题
抑制自由基反应，改进叔丁醇钾促进的 11C-甲基化策略，用于合成 α-11C-甲基氨基酸
DOI：
10.1002/jlcr.3259
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发表时间：
2015
影响因子：
1.8
通讯作者：
Saga T
中科院分区：
文献类型：
--
作者：
Suzuki C;Kato K;Tsuji AB;Zhang MR;Arano Y;Saga T
α-11 C-甲基氨基酸是生物成像研究的有用工具。然而，一个强大的程序标记的氨基酸尚未建立。在本研究中，我们对席夫碱活化的α-氨基酸衍生物的11 C-甲基化进行了优化，以用于各种α-11 C-甲基氨基酸的放射合成。2-氨基丁酸甲酯的二苯甲酮亚胺类似物在用叔丁醇钾（KOtBu）进行初始去质子化后，用[11 C]甲基碘进行11 C-甲基化。使用替代碱如四丁基氟化铵、三乙胺和1，8-二氮杂双环[5.4.0]十一碳-7-烯不会产生11 C-甲基化产物。此外，KOtBu-促进的席夫碱活化的氨基酸类似物的11 C-甲基化通过添加1，2，4，5-四甲氧基苯或2，2，6，6-四甲基哌啶-1-氧基（克里思）而增强，并且通过添加1，10-菲咯啉而抑制。这些结果表明，抑制KOtBu诱导的自由基生成可改善席夫碱活化氨基酸的α-11 C-甲基化。将KOtBu和克里思的混合物添加到席夫碱活化的氨基酸酯和[11 C]甲基碘的溶液中提供了最佳结果，并且叔丁基酯和二苯甲酮亚胺基团可以容易地水解以得到具有高放化转化率的所需α-11 C-甲基氨基酸。该方法也可用于其他α-11 C-甲基氨基酸的合成。
α‐11C‐Methyl amino acids are useful tools for biological imaging studies. However, a robust procedure for the labeling of amino acids has not yet been established. In this study, the11C‐methylation of Schiff‐base‐activatedα‐amino acid derivatives has been optimized for the radiosynthesis of variousα‐11C‐methyl amino acids. The benzophenone imine analog of methyl 2‐amino butyrate was11C‐methylated with [11C]methyl iodide following its initial deprotonation with potassiumtert‐butoxide (KOtBu). The use of an alternative base such as tetrabutylammonium fluoride, triethylamine, and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene did not result in the11C‐methylated product. Furthermore, the KOtBu‐promoted11C‐methylation of the Schiff‐base‐activated amino acid analog was enhanced by the addition of 1,2,4,5‐tetramethoxybenzene or 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) and inhibited by the addition of 1,10‐phenanthroline. These results suggest that inhibition of radical generation induced by KOtBu improves theα‐11C‐methylation of the Schiff‐base‐activated amino acids. The addition of a mixture of KOtBu and TEMPO to a solution of Schiff‐base‐activated amino acid ester and [11C]methyl iodide provided optimal results, and thetert‐butyl ester and benzophenone imine groups could be readily hydrolyzed to give the desiredα‐11C‐methyl amino acids with a high radiochemical conversion. This strategy could be readily applied to the synthesis of otherα‐11C‐methyl amino acids.