Design, Synthesis And Antibacterial Activities Of Erythromycin Derivatives

Erythromycin A has been routinely used to treat upper and lower respiratory tract infections, as well as social disease, skin and soft issue infections caused by gram-positive bacteria. However, erythromycin is hindered by its poor bioavailability, limited spectrum of activity and frequent gastrointestinal side effects. To overcome erythromycin A's limitation, the second-generation macrolide antibiotics, Clarithromycin and Azithromycin, were developed in 1980s. They have enjoyed great clinical success due to their enhanced antibacterial activity, expanded spectrum of activity, improved pharmacokinetic properties and attenuated gastrointestinal side effects as compared to erythromycin. Unfortunately, like erythromycin A, the second-generation macrolide antibiotics have poor activity against macrolide-resistant bacteria.Now, the intensive search for the third-generation macrolide antibiotics that overcome the problem of resistance have unveiled four classes of macrolides, termed ketolides, acylides, 4"-carbamates and 2,3-anhydrolides. Telithromycin, which is a ketolide representative and has come into market in 2000, shows good antibacterial activity against gram-positive macrolide-susceptive and -resistant organisms. It has fine acid-stability and is used in the treatment of respiratory tract infection. Cethromycin, which is a 6-O-substituated ketolide, shows improved antibacterial activity compared to Telithromycin and will come into market. These successes demonstrate that modifying the chemical structure of erythromycin is an important approach to finding novel macrolide antibiotics.Erythromycin A and Azithromycin were identified as lead compounds in this paper.