Manganese-Catalyzed Electrochemical Oxidation of Tryptophan-Containing Peptides and Indole Derivatives by O2

Abstract

Tryptophan oxidation products derived from the dioxygenation and monooxygenation of tryptophan derivatives exhibit a wide range of biological activities. Nature has evolved finely tuned biosynthetic pathways to oxidize tryptophan derivatives using molecular oxygen (O₂) as a co-substrate via enzymatic epoxidation steps. Nevertheless, the strategies involving these metalloenzymes are constrained by substrate specificity and the structural complexity of the enzymes. Driven by the practical demands for chemical conversions, there exists a longstanding quest for bioinspired catalysts guided by biomimetic catalytic principles in chemical transformations. In this regard, we herein present a single-step manganese-catalyzed aerobic electrochemical oxygenation of tryptophan-containing peptides (including peptide drugs) guided by the biomimetic catalytic principles to access the 3-hydroxy-oxindole- or 3-hydroxy-tetrazolo[1,5-a]indole-containing peptides and derivatives with broad functional group tolerances and high site selectivity under buffer conditions. Mechanistic investigations support that Mn-peroxo species are involved in the oxidation and the electricity contributes to the electron-transfer steps in the catalytic loop.