Progress in Lanthionine and Protected Lanthionine Synthesis

• Published in: Chemistry : a European journal Vol. 24; no. 58; pp. 15421 - 15441
• Main Authors: Denoël, Thibaut, Lemaire, Christian, Luxen, André
• Format: Journal Article Web Resource
• Language: English
• Published: Germany Wiley Subscription Services, Inc 17.10.2018; John Wiley & Sons
• Subjects: Amino acids; Antibiotics; Cell walls; Chemical synthesis; Chemistry; Chimie; Cystine; Drug development; Isomers; lanthionine; lantibiotic; Lantibiotics; Organic chemistry; Peptide antibiotics; Peptidoglycans; Physical, chemical, mathematical & earth Sciences; Physique, chimie, mathématiques & sciences de la terre; review; Serine; Stereoselectivity; sulfur; lantibiotic; lanthionine; sulfur; review; amino acids
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201801115

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. Non‐standard amino acid lanthionine, discovered through hydrolysis of wool, is mainly found in the family of cyclic peptide antibiotics called lantibiotics. Laboratory preparation of these bioactive compounds displaying interesting properties require efficient lanthionine synthesis. This review summarizes the chemical routes to lanthionine from multiple precursors, disclosing the experimental data and analysing the advantage and disadvantage of each method.