Visible‐Light‐Mediated Selective Arylation of Cysteine in Batch and Flow

• Published in: Angewandte Chemie International Edition 2017-10, Vol.56 (41), p.12702-12707
• Main Authors: Bottecchia, Cecilia, Rubens, Maarten, Gunnoo, Smita B., Hessel, Volker, Madder, Annemieke, Noël, Timothy
• Format: Article
• Language: English
• Subjects: Biocompatibility; Buffers; Communication; Communications; Cysteine; cysteine arylation; diazonium salts; microreactors; Phosphates; photochemistry; photoredox catalysis; Reaction time; Salts; Yttrium
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201706700

A mild visible‐light‐mediated strategy for cysteine arylation is presented. The method relies on the use of eosin Y as a metal‐free photocatalyst and aryldiazonium salts as arylating agents. The reaction can be significantly accelerated in a microflow reactor, whilst allowing the in situ formation of the required diazonium salts. The batch and flow protocol described herein can be applied to obtain a broad series of arylated cysteine derivatives and arylated cysteine‐containing dipeptides. Moreover, the method was applied to the chemoselective arylation of a model peptide in biocompatible reaction conditions (room temperature, phosphate‐buffered saline (PBS) buffer) within a short reaction time. Chemical modifications of peptides: The mild visible‐light‐mediated arylation of cysteine relies on the use of eosin Y as a metal‐free photocatalyst and aryldiazonium salts as arylating agents. The batch and flow method afforded a series of arylated cysteine derivatives and arylated cysteine‐containing dipeptides. A model peptide has been chemoselectively arylated under biocompatible reaction conditions.