Synthesis of the tris-Amino Acid Labionin through a Contrasteric Aziridination and Ring-Opening Sequence

The non-proteinogenic tris-amino acid labionin was discovered in 2010 and since has been described in many natural products, defining an entire family of lanthipeptides. The unusual amino acid is biosynthetically produced by the sequential condensation of a cysteine onto two dehydroalanines. An attempt in 2011 to synthesize the amino acid monomeric unit was unsuccessful yet served as a valuable foundation and guide to the present work. A recently disclosed methodology for the selective opening of aziridines by mercaptan nucleophiles was applied to another methodology for contrasteric aziridination, thus enabling a short synthesis of challenging and elusive labionin.