Synthesis of a Cyclic Pentapeptide Mimic of the Active Site His-Tyr Cofactor of Cytochrome c Oxidase

Arylboronic acid based technology provides a mild, regioselective, and nontoxic N-arylation procedure for accessing the unusual N-arylated side chain histidine found in the active site of cytochrome c oxidase (CcO). The N-arylated histidine is elaborated to the complete cytochrome c oxidase cyclic pentapeptide cofactor. Molecular modeling of the cofactor provides insight into the dynamic character of the N-aryl bond.