Allenone-Mediated Racemization/Epimerization-Free Peptide Bond Formation and Its Application in Peptide Synthesis

• DOI: 10.1021/jacs.1c04614
• Publication Date: 2021-06-30T20:14:49Z
• Authors: Zhengning Wang; Xuewei Wang; Penghui Wang; Junfeng Zhao
• Keywords: Racemization; Peptide Synthesis; Epimer; Peptide bond; Peptidomimetic

Allenone has been identified as a highly effective peptide coupling reagent for the first time. The bond was formed with an α-carbonyl vinyl ester key intermediate, formation and subsequent aminolysis of which proceed spontaneously in racemization-/epimerization-free manner. allenone not only is synthesis simple amides dipeptides but also amenable to fragment condensation solid-phase (SPPS). robustness allenone-mediated showcased incisively by carfilzomib, involved rare N C elongation strategy. Furthermore, successful model difficult ACP (65-74) on solid support suggested that this method compatible SPPS. This combines advantages conventional active esters reagents, while overcoming disadvantages both strategies. Thus, strategy represents disruptive innovation synthesis.