Synthesis of tetrazole analogues of amino acids using Fmoc chemistry: isolation of amino free tetrazoles and their incorporation into peptides

An efficient synthesis of tetrazole analogues of amino acids starting from Nα-Fmoc amino acid in a three-step protocol is reported. The free amino tetrazoles were obtained in good yields and with excellent purity after removal of the Fmoc group. The synthesis of analogues of aspartic and glutamic acids in which the 5-tetrazolyl moiety is inserted at the β/γ carboxyl group starting from Fmoc-Asn and Fmoc-Gln and the incorporation of these tetrazoles into peptides are also described.

Graphical abstractTetrazole analogues of amino acids have been prepared employing Fmoc chemistry and [2+3] cycloaddition. Tetrazole rings have also been incorporated into the side chains of Asp/Glu via a similar procedure and utilized for peptide synthesis.Download full-size image