Convenient synthesis of a head-to-tail cyclic peptide containing an expanded ring

Here we describe a rapid and efficient solid-phase synthesis of a 29-mer cyclic antibacterial peptide 1, currently under pharmaceutical development. The linear peptide was assembled by standard Fmoc chemistry on an Fmoc-Asp(resin)-ODmab carrier. Intramolecular on-resin head-to-tail cyclization was enabled after selective deprotection of the Asp α-carboxy protecting group with 2% hydrazine–DMF at room temperature.