Peptide thioacylation with high stereochemical preservation

dipeptide thioamide model system, Boc-Leu-psi[CSNH]-Met-OMe, was used for evaluating the preservation of amino acid stereochemistry during thioacylation utilizing amino monothio acids. The LL and DL peptide diastereomers were separated by use of high performance capillary electrophoresis (micellar electrokinetic capillary chromatography). The described thioacylation method combines monothio acids with coupling reagents of the PyBOP-family for generating active thiono esters with low-levels of enantiomerisation (< 2%). The best results in terms of stereochemical preservation and yield were obtained with PyNOP, a 6-nitro analog of PyBOP. The successful activation of thiobenzoic acid with all four coupling reagents extended the scope of the method to include aryl monothio acids.