Synthesis of Peptide-^αThiophenylesters for Native Chemical Ligation

Significance

A direct on-resin preparation method of peptide-^αthiophenylester was reported. Gly-MBHA-resin 1 was treated with (S-tritylmercapto­phenyl)acetic acid in the presence of HBTU and DIPEA to give (tritylmercaptophenyl)acetyl glycine resin 2. After removal of the trityl group of 2 by TFA, the resin-bound peptide-thiophenylester 4 was prepared from thiophenol 3 by using modified in situ neutralization solid-phase peptide-synthesis protocols (see the Supporting Information of this article for further details). Cleavage from the resin support by HF gave the desired peptide-^αthio­phenylester 5. The resulting peptide-^αthio­phenylesters enhanced the ligation reaction with a Cys-peptide compared to the standard peptide-αthioalkylester.