Visible Light-Mediated Functionalization of Selenocystine-Containing Peptides

A straightforward and atom-economic method for the functionalization of short selenocystine-containing peptides is presented. This method is shown to be tolerant to unprotected peptides. The detailed protocol is based on the generation of a selenium radical via visible light-initiated reaction in the presence of transition metal-free photocatalyst. The selenium radical is further oxidized to an electrophile and trapped by N-heterocycles. The mechanism is confirmed by NMR, HRMS, UV, EPR and cyclic voltammetry (CV) experiments and photocatalyst emission quenching studies. A visible light-initiated reaction is employed for the synthesis of selenocysteine-containing indole-based macrocycles via intramolecular Se-C bond formation.

Automated summary

A straightforward and atom-economic method has been developed for the functionalization of short selenocystine-containing peptides, which shows good tolerance to unprotected peptides. This method is based on the generation of a selenium radical via visible light-initiated reaction in the presence of transition metal-free photocatalyst, and further oxidized to an electrophile that is trapped by N-heterocycles for functionalization. Mechanism confirmation includes NMR, HRMS, UV, EPR and cyclic voltammetry experiments as well as photocatalyst emission quenching studies.