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.
Wilbur
D S
DS
Department of Radiation Oncology, University of Washington, Seattle 98195.
Hamlin
D K
DK
Srivastava
R R
RR
Burns
H D
HD
D007457:Iodine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods*; D010455:Peptides / Q000138:chemical synthesis*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D014220:Trialkyltin Compounds / Q000138:chemical synthesis*
D007457:Iodine Radioisotopes; D010455:Peptides; D014220:Trialkyltin Compounds; C085787:tert-butyloxycarbonyl-4-(tri-n-butylstannyl)-phenylalanine tetrafluorophenyl ester; D010649:Phenylalanine; C049181:4-iodophenylalanine