Convenient preparation of 4-(tetrazol-5-yl)-phenylalanine for use in Fmoc-based solid-phase peptide synthesis

To create a novel amino acid incorporating both acidic and aromatic features, trimethyltin azide was used to synthesize l-4-(tetrazol-5-yl)-phenylalanine (Tpa) and the corresponding d,l racemate by [3+2] cycloadditition of azide to the nitrile group of corresponding 4-cyanophenylalanine analogs. Nα-Fmoc-Tpa derivatives, possessing no protection of the tetrazole ring, were well-behaved monomers in the synthesis of a model peptide using standard solid-phase methods.