Penicillins, development classical cephalosporins

This section aims to complete the picture on the studies summarized in CHEC-II(1996) on the synthesis of classical cephalosporins, describing the main cephalosporin methodologies developed during the last decade. In CHEC-II(1996), an approach was presented for the formation of the cephalosporin framework bearing various heteroatom and carbon substituents at the C-3 position, which relies on a sequential addition/cyclization of allenoate 70, derived from penicillin G. 

Potent antibiotics [1] have been developed by systematic modifications of RS and X substituents of the naturally-occurring penicillins 1 and cephalosporins 2. Concomitantly, the intensive search for new microbial P-lactams has led to the discovery [1] of active compounds such as thienamycin 3, clavulanic acid 4 and monobactams 5 (Scheme 1). The non-classical structure of these compounds led to a re-evaluation of the structural requirements for biological activity, and to the synthesis of new classes of P-lactam antibiotics such as penems 6 [5], oxacephems 7 [6] and oxamazins 8 [7]. 

The development of antibacterial chemotherapy during the past 75 years has spearheaded the successful use of today s drugs to combat bacterial infections. Studies in (3-lactam chemistry were stimulated when (3-lactam ring, the four membered heterocycle, was recognized as a key structural feature as well as a key therapeutic feature of the bicyclic (3-lactam antibiotics such as penicillins, cephalosporins, and other classical antibiotics. The last two decades have registered the discovery of several nonclassical bicyclic (3-lactam antibiotics, e.g., thienamycin and carba-penems of natural origin like olivanic acids, carpetimycin, pluracidomycin, and aspareomycins. 

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