Systematic Investigation on Acid-Catalyzed Truncation of N-Acylated Peptoids

Peptoids have emerged as a useful alternative to peptides. However, <i>N</i>-acylated peptoids have occasionally undergone truncation at the terminal peptoid unit under acidic conditions. We previously reported on the mechanistic and electronic aspects of the acid-catalyzed truncation of <i>N</i>-acylated peptoids. To gain further insight, we systematically investigated the conformational and electronic effects of the terminal side chains of peptoids. The <i>n</i>→<i>π</i>* interaction, based on <i>cis/trans</i>-amide bond conformation, is considered to be one of the determining factors. In this study, it was demonstrated that both conformational and electronic factors contribute to this unusual truncation.