Copper-Catalyzed <i>N</i>-Arylation of Semicarbazones for the Synthesis of Aza-Arylglycine-Containing Aza-Peptides

Parallel synthesis of 13 aza-arylglycine peptides, based on the hexapeptide sequence of Growth Hormone Releasing Peptide-6 (GHRP-6), was accomplished via selective <i>N</i>-arylation of a semicarbazone peptide building block anchored on Rink amide resin. Aza-peptides possessing aza-indolylglycine and aza-imidazoylglycine residues were obtained through use of the corresponding heteroaryl iodides, yielding, respectively, aza-Trp and aza-His peptidomimics. CD spectroscopy indicated the propensity for aza-peptides, containing aza-arylglycines at the Trp⁴ position of the GHRP-6 sequence, to adopt β-turns.