Halogenase-Assisted Alkyne/Aryl Bromide Sonogashira Coupling for Ribosomally Synthesized Peptides
Nirmal Saha, F. N. U. Vidya, Ramon Xie, Vinayak Agarwal
Abstract
We describe the enzymatic bromination of ribosomally synthesized peptides and develop protocols for Sonogashira coupling of peptidic aryl bromides with a panel of alkynes. Using this workflow, entirely new chemical handles are introduced onto ribosomal peptides, including but not limited to terminal alkynes, which enable further diversification via alkyne-azide click chemistry. Regiospecific enzymatic installation of the aryl bromide circumvents genetic code expansion and passivation of other reactive handles on the peptide chain, representing the applicability of biocatalysts in peptide modification chemistry.
Topics & Concepts
ChemistryAlkyneSonogashira couplingArylCombinatorial chemistryBromideCoupling (piping)Organic chemistryPalladiumEngineeringAlkylMechanical engineeringCatalysisClick Chemistry and ApplicationsChemical Synthesis and AnalysisCatalytic C–H Functionalization Methods