Optimized monomer-based synthesis of poly-N-amino peptides

We report an optimized protocol for the solid-phase synthesis of backbone-N-aminated peptides. Electrophilic N-amination of amino acid zwitterions provides crude -hydrazino acids that can be used directly in SPPS. In situ formation of Fmoc-protected amino acid chlorides with Ghosez’s reagent enables base-free couplings to -hydrazino acids on an automated system. TFA-free cleavage and global deprotection affords poly-N-amino peptides in high crude purity and in a fraction of the time required by previously reported methods.