Wilbur D S, Hamlin D K, Srivastava R R, Burns H D
Department of Radiation Oncology, University of Washington, Seattle 98195.
Bioconjug Chem. 1993 Nov-Dec;4(6):574-80. doi: 10.1021/bc00024a024.
An investigation to prepare a phenylalanine derivative which could be radioiodinated and used directly in peptide synthesis was conducted. N-Boc-p-(tri-n-butylstannyl)-L-phenylalanine tetrafluorophenyl ester was targeted and synthesized from N-Boc-p-iodo-L-phenylalanine. The requisite aryl stannylation reaction was found to be best conducted using the phenylalanine methyl ester. Thus, N-Boc-p-iodo-L-phenylalanine methyl ester was prepared and stannylated using bis(tributyltin) and tetrakis-(triphenylphosphine)palladium(0) in refluxing toluene to prepare N-Boc-p-(tri-n-butylstannyl)-L-phenylalanine methyl ester. Demethylation with aqueous base was accomplished without racemization to yield N-Boc-p-(tri-n-butylstannyl)-L-phenylalanine. Preparation of the targeted stannylphenylalanine tetrafluorophenyl ester was then accomplished using 2,3,5,6-tetrafluorophenol and 1,3-dicyclohexyl-carbodiimide in anhydrous THF. Iodination and radioiodination reactions of the targeted compound were conducted in MeOH/1% HOAc to yield 83-95% of the desired N-Boc-p-[*I]iodo-L-phenylalanine tetrafluorophenyl ester.
开展了一项制备可进行放射性碘化并直接用于肽合成的苯丙氨酸衍生物的研究。以N-叔丁氧羰基-p-(三正丁基锡烷基)-L-苯丙氨酸四氟苯酯为目标化合物，由N-叔丁氧羰基-p-碘-L-苯丙氨酸合成得到。发现所需的芳基锡化反应使用苯丙氨酸甲酯进行效果最佳。因此，制备了N-叔丁氧羰基-p-碘-L-苯丙氨酸甲酯，并在回流的甲苯中使用双(三丁基锡)和四(三苯基膦)钯(0)进行锡化反应，制备N-叔丁氧羰基-p-(三正丁基锡烷基)-L-苯丙氨酸甲酯。用水性碱进行脱甲基反应时未发生消旋化，得到N-叔丁氧羰基-p-(三正丁基锡烷基)-L-苯丙氨酸。然后在无水四氢呋喃中使用2,3,5,6-四氟苯酚和1,3-二环己基碳二亚胺制备目标锡烷基苯丙氨酸四氟苯酯。在甲醇/1%醋酸中进行目标化合物的碘化和放射性碘化反应，得到83 - 95%的所需N-叔丁氧羰基-p-[*I]碘-L-苯丙氨酸四氟苯酯。
