The occurrence of ansamers in the synthesis of cyclic peptides

α-Amanitin is a bicyclic octapeptide composed of a macrolactam with a tryptathionine cross-link forming a handle. Previously, the occurrence of isomers of amanitin, termed atropisomers has been postulated. Al-though the total synthesis of α-amanitin has been accomplished this aspect still remained unsolved. We performed the synthesis of amanitin analogues, accompanied by in-depth spectroscopic, crystallographic and molecular dynamics studies. The data unambiguously confirmed the synthesis of two amatoxin-type isomers, for which we propose the term ansamers. The natural structure of the P-ansamer can be ansa-selectively synthesized using an optimized synthetic strategy. We believe that the newly described terminology does also have implications for many other peptide structures, e.g. norbornapeptides, lasso peptides, tryptorubins and others, and helps to unambiguously describe conformational isomery of cyclic peptides.