N-Fmoc-Peptide azides: Synthesis, isolation, characterization and utility in the extension of peptide chains

The chemical approaches to the synthesis of peptides and proteins by the azide coupling 2 have turned out to be one of the safest methods of avoiding racemization. The azide procedure has been widely used for the coupling of difficult amino acid residues such as His, Thr, Ser, Trp, etc., and also particularly for the condensation of peptide fragments using both the maximum and minimum protection strategy in the solution phase synthesis of peptides. Yajima’s successful synthesis of a 124 residue protein ribonuclease A utilizing about thirty small segments as key intermediates by the azide method following the segment condensation approach in solution is a landmark achievement in the history of chemical synthesis of proteins. Similar strategy has been employed in the synthesis of several other polypeptides and proteins. Their synthesis mainly involves the generation of N-Bocor Z-peptide azides as key intermediates.