Arylglycine: A Focus on Amino Acid Preparation and Peptide Synthesis

Amino acids are the principal constituent of peptides and proteins. The ever-going expansion beyond non-canonical amino acids is one of the challenges in peptide medicinal chemistry and protein engineering. Amongst non-canonical amino acids, natural peptides provide an extraordinary source of inspiration; particularly in the family of non-ribosomal peptides. Amongst a large variety of unnatural amino acids, the family of arylglycine is exemplified in natural products by phenylglycine (Phg), 4-hydroxyphenylglycine (Hpg) and 3,5-dihydrophenylglycine (Dpg). Nevertheless, their usage in peptide and protein remains quite limited due to synthetic issues, namely tedious amino acid preparation and poor compatibility with solid-phase peptide synthesis (SPPS). This review aims to re-group the strategies developed over the years to provide access to arylglycines compatible with peptide synthesis.