Here, we report that linear peptides with a reactive N-terminal β-keto amide functionality can be synthesized ribosomally using in vitro translation (IVT), and that peptides carrying an N-terminal β-keto amide are substrates for Friedländer reactions capable of generating a diverse set of quinoline-peptide hybrid products. Reaction of the N-terminal β-keto amide with an appropriately substituted 2-aminobenzophenone provides a Friedländer product possessing a stable atropisomeric axis whose structure could be characterized by NMR and X-ray crystallography. Finally, synthetic or IVT peptides carrying both an N-terminal β-keto amide and an internal kynurenine residue are substrates for intramolecular Friedländer macrocyclization reactions that embed a quinoline pharmacophore into the peptide backbone. The introduction of simple ketide building blocks into ribosomal synthesis and their post-translational derivatization with carbonyl chemistry expands the structural and stereochemical diversity available to genetically encoded peptides and provides a paradigm for the programmed synthesis of peptide-derived materials that more closely resemble complex natural products.