Lelievre D., Terrier V. P., Delmas A. F. and Aucagne V.
Organic letters (2016 18 (5) 920-923 - doi : 10.1021/acs.orglett.5b03612
publié le , mis à jour le
The Fmoc-based solid phase synthesis of C-terminal cysteine-containing peptides is problematic, due to side reactions provoked by the pronounced acidity of the Calpha proton of cysteine esters. We herein describe a general strategy consisting of the postsynthetic introduction of the C-terminal Cys through a key chemoselective native chemical ligation reaction with N-Hnb-Cys peptide crypto-thioesters. This method was successfully applied to the demanding peptide sequences of two natural products of biological interest, giving remarkably high overall yields compared to that of a state of the art strategy.