Progress in Lanthionine and Protected Lanthionine Synthesis.

Lanthionine (Lan), a non-proteinogenic natural amino acid, is an essential component of peptidoglycan found in the cell wall of Fusobacterium species. Lan and β-methyllanthionine are also key constituents in lantibiotics, a prevalent class of peptide antibiotics. The development of those new antibacterial drugs with enhanced properties is the focus of recent research. Since multiple isomers of Lan are possible, a regio- and diastereoselective synthesis is challenging. This comprehensive review summarizes the known chemical syntheses of lanthionine from various precursors (e.g., β-chloroalanine, cystine, dehydroalanine, β-iodoalanine, aziridine, serine lactone, sulfamidate) since 1941. Methods for preparation of unprotected, protected, orthogonally protected, and mutually orthogonally protected lanthionine with relevant experimental details and perspectives on their usefulness are provided. The potential of these Lan derivatives is illustrated by one recent application.