Epimerization-free access to C-terminal cysteine peptide acids, carboxamides, secondary amides, and esters via complimentary strategiesElectronic supplementary information (ESI) available. See DOI: 10.1039/c7sc03553e

• Main Authors: Arbour, Christine A, Kondasinghe, Thilini D, Saraha, Hasina Y, Vorlicek, Teanna L, Stockdill, Jennifer L
• Format: Article
• Language: English
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c7sc03553e

C-Terminal cysteine peptide acids are difficult to access without epimerization of the cysteine α-stereocenter. Diversification of the C-terminus after solid-phase peptide synthesis poses an even greater challenge because of the proclivity of the cysteine α-stereocenter to undergo deprotonation upon activation of the C-terminal carboxylic acid. We present herein two general strategies to access C-terminal cysteine peptide derivatives without detectable epimerization, diketopiperazine formation, or piperidinylalanine side products. We present a convenient method for the diversification of peptides bearing cysteine at the C-terminus that proceeds to form a variety of carboxylic acid, carboxamide, 2° amide, and ester terminated peptides without any detectable epimerization of the α-stereocenter.