High-Yielding Staudinger Ligation of a Phosphinothioester and Azide To Form a Peptide

The Staudinger ligation can be used to couple a peptide with a C-terminal phosphinothioester to another with an N-terminal α-azido group to form a single peptide that contains no residual atoms. Here, diphenylphosphinomethanethiol thioesters are shown to give high isolated yields for this transformation. This finding provides precedent for a powerful and versatile new method for the total synthesis of proteins.