Automation of the Azapeptide Submonomer Synthesis Method.

The automation of the azapeptide submonomer synthesis procedure is reported. All steps for on-resin aza-amino acid synthesis, including semicarbazone incorporation, alkylation, deprotection, and semicarbazide acylation were adapted for use on a commercially available peptide synthesizer. Key requirements for success included the use of a stable isocyanate precursor for the semicarbazone installation, the use of stable reagents in DMF, and elimination of cooling steps. The synthesis of > 30 azapeptides was accomplished using our optimized automated submonomer azapeptide synthesis procedure.