Joseph O'sullivan

Naturally Occurring Monobactams

Publisher Summary The naturally occurring monobactams discovered to date are uniformly poor antibiotics that afford in themselves no opportunity for clinical utility. However, the monobactam nucleus and analogs with a variety of substituents in the 1-, 3-, and 4-positions of the azetidinone ring are readily accessible by synthesis. This highly active area of research has been the subject of recent reviews. A number of synthetic analogs that have excellent antimicrobial activity in vivo have been developed. Aztreonam, the first synthetic monobactam to undergo clinical trials, has entered the market, and a second synthetic monobactam, AMA 1080, is presently undergoing clinical trials. Both of these antimicrobial agents are useful for treating gram-negative bacterial infections by parenteral administration. An orally active prodrug, SQ 82,531, has been described and is presently undergoing clinical evaluation. This agent illustrates an alternative mode of providing activation of the β-lactam and (after enzymatic hydrolysis to SQ 82,291) an anionic binding site. Because of the great synthetic flexibility inherent in the monobactam system, it is probable that further clinically useful antimicrobial agents will follow.