Preparation of Constrained Unnatural Aromatic Amino Acids via Unsaturated Diketopiperazine Intermediate

Unnatural aromatic amino acids are useful tools in drug discovery, since their insertion in bioactive peptide sequences can change the side chains spatial orientation, the backbone conformation and above all, their bioactivity. In this communication, we propose a straightforward method to synthesize 2',6'-dimethyl-tyrosine and 2',6'-dimehylphenyl-alanine derivatives as handling building blocks for peptide synthesis via unsaturated diketopiperazine (DKP) intermediate.