A Synthetic Approach to a Peptide α‐Thioester from an Unprotected Peptide through Cleavage and Activation of a Specific Peptide Bond by N‐Acetylguanidine

A different route to peptide α-thioesters through a new peptide-bond-cleavage method at a cysteine residue by S-thiocarbonylation and subsequent treatment with N-acetylguanidine is described (see scheme). The resultant peptidyl-N-acetylguanidine can be converted into the corresponding peptide α-thioester and is also usable as an alternative to a peptide α-thioester. This method allows efficient kinetically controlled ligation in the presence of thiols.