2-Mercaptophenylboronic acid: a superior alternative to 2-mercaptoethanol for thioester hydrolysis

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 the proposed reaction pathway. These findings highlight the potential of 2-MPBA as a practical alternative for thioester hydrolysis under mild conditions.