Mini Review on Synthetic Approaches to Thienamycin

In this review, progress in the development and synthesis of thienamycin and carbapenem β-lactams is described. Thienamycin is one of the most prominent members of the carbapenem class of antibiotics, containing a fused β-lactam ring responsible for its antibacterial effect. Various synthetic methods reported for the preparation of thienamycin are discussed. Several approaches have been reported for generating optically active thienamycin, including intramolecular N-C4 cyclization, radical cyclization, and others. All of these methods are versatile and valuable for synthesizing precursors of important β-lactam antibiotics and other heterocycles. Several chiral approaches that form important intermediates for biologically active (-)- and (+)-thienamycin are captured here. The optically active β-keto ester, an essential intermediate for the preparation of thienamycin, is obtained via an enantioselective [3+2] cycloaddition reaction between a chiral nitrone and benzyl crotonate, a valuable synthetic pathway. Other promising pathways have also extended stereospecific control to key stereocenters in thienamycin. Numerous successful applications of these methods are expected in the near future for the synthesis of thienamycin and its analogs. This review focuses on the development of various new chemical entities based on thienamycin and its analogs for future development. A literature survey was carried out to understand overall trends in the synthesis of thienamycin and related drugs.