Fmoc-SPPS chemistry compatible approach for the generation of (glyco)peptide aryl thioesters

A new approach is described for the general Fmoc-based solid-phase synthesis of (glyco)peptide aryl thioesters. A peptide alkyl oxoester obtained by standard Fmoc-based chain elongation undergoes an O-to-S acyl shift, and is followed by alkyl thioester exchanges with a large excess of aryl thiol, affording the corresponding peptide aryl thioester. The newly developed methodology is useful for the chemical synthesis of post-translationally modified proteins because of its compatibility with standard Fmoc-SPPS conditions. In addition, the peptide aryl thioesters are essential intermediates for chemical synthesis of proteins by kinetically controlled convergent strategy.