Non-classical p-lactams

L. D. Cama, B. G. Christensen (1978). Structure-activity relationships of non-classical P-lactam... 

Coll M, Frau J, Donoso J, Munoz F. PM3 study of reactivity of non-classical P-lactam structures. J Mol Struct THEOCHEM 1999 493 287-299. 

In this essay, we discuss studies concerning the synthesis of non classical P-lactam antibiotics using the esto enolate imine condoisation route. As starting imines, we have particularly studied T -trimethylsilylimines (Scheme 2). 

The stereoselective synthesis of classical trinems (fused tricyclic systems having the azetidin-2-one nucleus fused through the N-C4 bond) <98MI347> and the chemistry of non-classical polycyclic P-lactams have been reviewed <00T5743>. 

A review discusses the stereocontrol led synthesis of polycyclic-P-lactams with non-classical structure <02MI245>. 

Finally, it may be worthwhile to point out that one of the most successful chemotherapeutic drugs provided by nature may be considered as a non-classical active-site-directed irreversible inhibitor This drug is penicillin (70). As a non-classical antimetabolite of D-alanyl-D-alanine, it first forms a reversible complex with the enzyme peptidoglycan transpeptidase, and then by a ringopening reaction of its p-lactam moiety, it forms a covalently linked penicil-loyl-enzyme complex97. However, the reaction involves the acylation of a sulfhydryl group in the active site of the enzyme in this respect, 70 resembles the classical-type endoalkylating antimetabolites, azaserine and DON (8 and 9, see Section 2.2.). Some of the more recently discovered antibiotics and natural products from plants with antitumor activity (e.g., camptothecin) are... 

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]. 

---