Synthesis and antibacterial study of anhydrotetracycline derivatives

Yong Wang; He Wu; Guangguang Yang; Karuppu Selvaraj; Gang Chen

doi:10.1016/j.bmcl.2024.130090

Synthesis and antibacterial study of anhydrotetracycline derivatives

Bioorg Med Chem Lett. 2024 Dec 28:118:130090. doi: 10.1016/j.bmcl.2024.130090. Online ahead of print.

Authors

Yong Wang¹, He Wu¹, Guangguang Yang¹, Karuppu Selvaraj¹, Gang Chen²

Affiliations

¹ Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
² Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China. Electronic address: gchen2018@sjtu.edu.cn.

PMID: 39736277
DOI: 10.1016/j.bmcl.2024.130090

Abstract

A novel and new type of tetracycline with a different mechanism of action was necessary, due to the drug resistance of existing tetracyclines. This study outlines the synthesis and antibacterial evaluation of anhydro-tetracycline derivatives, which are unconventional tetracyclines with unique mechanisms of action. These derivatives include C4-NH₂, C4-OH, and C9-substituted variations, and our synthetic approach focuses on semi-synthesis using natural tetracyclines as the starting precursors. Several derivatives of C4-NH₂, C4-OH, and C9-substituted compounds have demonstrated effective antibiotic activity against both Gram-positive and Gram-negative bacteria.

Keywords: Antibacterial; SAR study; Semi-synthesis; Tetracycline.