2-Mercaptophenylboronic Acid: A Superior Alternative to 2-Mercaptoethanol for Thioester Hydrolysis

Abstract

Herein, we demonstrate that 2-mercaptophenylboronic acid promotes the hydrolysis of peptide alkyl thioesters via thiol-thioester exchange to form a reactive aryl thioester intermediate, followed by borate-assisted hydrolysis of the intermediate. This reagent hydrolyses thioesters rapidly compared to formal hydrolysis using 2-mercaptoethanol under neutral conditions. Density functional theory calculations provide qualitative insight into the relative feasibility of proposed reaction pathway.These findings highlight the potential of 2-MPBA as a practical alternative for thioester hydrolysis under mild conditions.