Synthesis and radioiodination of N-Boc-p-(tri-n-butylstannyl)-L-phenylalanine tetrafluorophenyl ester: preparation of a radiolabeled phenylalanine derivative for peptide synthesis.

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.