Visible Light‐Mediated Functionalization of Selenocystine‐Containing Peptides

Abstract

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.

Visible Light‐Mediated Synthesis of Se−S Bond‐Containing Peptides

“…The highest selectivity and conversion of the starting materials was achieved employing Rose Bengal (RB). Other catalysts were: (i) less effective (bis[2‐(4,6‐difluorophenyl)pyridinato‐C 2 , N ](picolinato)iridium(III) (FIrPic)); (ii) induced formation of the respective alkyl seleninic acid which subsequently led to deselenylation by elimination of H 2 SeO 3 providing dehydroalanine (Dha) peptide [21] (Ru(bpy) 3 Cl 2 , 2,4,5,6‐tetrakis(9 H ‐carbazol‐9‐yl) isophthalonitrile (4‐CzIPN), 9‐mesityl‐10‐methylacridinium tetrafluoroborate, ethyl eosin, fluorescein), or (iii) failed to initiate the reaction (5‐carboxytetramethylrhodamine). Performing the reaction in methanol and ethanol resulted in lower conversion of 1 a in the given time.…”

“…Besides, a small signal of selenonic acid 6 b (δ 1050.8 ppm) was also detected in the 77 Se NMR spectra (Figure S1). The alkyl seleninic acid 6 a is too unstable to be isolable, it delivers 7 via deselenylation [21] . The use of t BuOOH led to the formation of 7 in 2 h as well.…”

“…The alkyl seleninic acid 6 a is too unstable to be isolable, it delivers 7 via deselenylation. [21] The use of tBuOOH led to the formation of 7 in 2 h as well.…”

“…[20] Recently, we have reported an efficient method for the functionalization of SeÀ Se bond-containing peptides, based on the generation of a selenium radical via visible light-initiated reaction. [21] As a continuation of our research related to development of methods for modification of selenocysteine [22][23] (Sec) and cysteine [24] peptides, here we report a simple protocol for preparation of SeÀ S bond-containing peptides using visible light-initiated reaction.…”

“…Selenyl radical is quickly oxidized to selenyl electrophile that reacts with H 2 O 2 forming alkyl seleninic acid 6 and BocÀ DhaÀ GlyÀ OBn 7 (Scheme 4). [21] H 2 O 2 is produced from singlet oxygen reaction with water.…”