An Fmoc compatible, O to S shift-mediated procedure for the preparation of C-terminal thioester peptides

We report a practical 2-hydroxy-3-mercapto-propionic acid (Hmp)/2-methylpiperidine (2-MP) based Fmoc chemistry procedure to prepare the C-terminal Hmp peptides, which serve as the precursors of C-terminal thioester peptides. The subsequent O to S acyl shift and thiol-exchange mediated thioester conversion of the crude precursor peptides can be accomplished smoothly under mild conditions to provide the desired thioester peptides with good yield and high quality. This is a highly adaptable approach, and we envision its broad application in the preparation of C-terminal thioester peptides.