Design And Synthesis Of 14-Membered Macrolide Derivatives Against Resistant Bacteria

Macrolide antibiotics have been widely used for the treatment of bacterial infections for nearly sixty years since the early 1950s and have been playing an important role in the clinic. With the extensive use of the antibiotics, especially abuse, the serious problem of bacterial resistance has happened in the clinic, which results in a decrease in curative effect, and even no effect.The macrolides' mechanism of action is that they can bind to the target of A2058 in domain Vof the 23S rRNA in 50S subunit of bacterial ribosome and exert their antibacterial activities by inhibiting protein synthesis of bacteria. However, the main mechanism of the bacterial resistance to macrolides is the modification of the target, the methylation of N~6 on A2058 by peptidyl transferase coded by gene erm, which makes the target not to bind to macrolides. Consequently, the bacterial resistance appears.In order to enhance the activities of macrolides against resistant bacteria, a great number of macrolide derivatives have been synthesized through the structural modification. Among them, the best successful example is ketolides which produce not only the potent antibacterial activities by binding to the target of A2058 in domain V through 5-desosamine, but also the strong activities against resistant bacteria by binding to the target of A752 through their side chains.