Progress in Lanthionine and Protected Lanthionine Synthesis.

Area of Science:

• Biochemistry
• Organic Chemistry
• Medicinal Chemistry

Background:

• Lanthionine (Lan) is a non-proteinogenic amino acid vital for peptidoglycan in Fusobacterium species.
• Lan and its derivatives are key components of lantibiotics, a class of peptide antibiotics.
• Research is focused on developing new antibacterial drugs with improved properties.

Purpose of the Study:

• To comprehensively review known chemical syntheses of lanthionine since 1941.
• To detail methods for preparing various lanthionine derivatives, including protected and unprotected forms.
• To provide perspectives on the utility of these lanthionine derivatives in drug development.

Main Methods:

• Review of literature on chemical syntheses of lanthionine from diverse precursors.
• Compilation of methods for regio- and diastereoselective synthesis of lanthionine isomers.
• Inclusion of experimental details for preparing unprotected, protected, and orthogonally protected lanthionine.

Main Results:

• Summarizes lanthionine synthesis from precursors like β-chloroalanine, cystine, dehydroalanine, and serine lactone.
• Details methods for creating various lanthionine derivatives with different protection strategies.
• Highlights the potential applications of these lanthionine derivatives, exemplified by a recent use case.

Conclusions:

• Regio- and diastereoselective synthesis of lanthionine remains a significant challenge.
• Various chemical synthesis routes provide access to diverse lanthionine derivatives.
• Lanthionine derivatives hold promise for the development of novel antibacterial agents.