Inhibition of radical reactions for an improved potassium tert-butoxide-promoted (11) C-methylation strategy for the synthesis of α-(11) C-methyl amino acids.
| Autor: | Suzuki C; Diagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan; Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan., Kato K, Tsuji AB, Zhang MR, Arano Y, Saga T |
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| Jazyk: | angličtina |
| Zdroj: | Journal of labelled compounds & radiopharmaceuticals [J Labelled Comp Radiopharm] 2015 Mar; Vol. 58 (3), pp. 127-32. Date of Electronic Publication: 2015 Feb 18. |
| DOI: | 10.1002/jlcr.3259 |
| Abstrakt: | α-(11) C-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, the (11) C-methylation of Schiff-base-activated α-amino acid derivatives has been optimized for the radiosynthesis of various α-(11) C-methyl amino acids. The benzophenone imine analog of methyl 2-amino butyrate was (11) C-methylated with [(11) C]methyl iodide following its initial deprotonation with potassium tert-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 the (11) C-methylated product. Furthermore, the KOtBu-promoted (11) C-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 the α-(11) C-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 [(11) C]methyl iodide provided optimal results, and the tert-butyl ester and benzophenone imine groups could be readily hydrolyzed to give the desired α-(11) C-methyl amino acids with a high radiochemical conversion. This strategy could be readily applied to the synthesis of other α-(11) C-methyl amino acids. (Copyright © 2015 John Wiley & Sons, Ltd.) |
| Databáze: | MEDLINE |
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