Current Medicinal Chemistry - Volume 11, Issue 14, 2004

The importance of the stereodivergent synthesis of chiral and achiral β-lactams is ever increasing in connection with the structure-activity relationship study and the development of new derivatives of the β-lactam antibiotics and inhibitors of β- lactamases. Due to the increased bacterial resistance, there has been effort expended to prepare new structural types having the 2-azetidinone ring as a common featur Read More

The synthesis of oxacephalotin and oxacephamandol, which are more active than natural, sulfurcontaining congeners, and the isolation of clavulanic acid, a potent inhibitor of β-lactamase enzymes, directed attention of many academic and industrial laboratories the synthesis of oxygen analogues of penicillins and cephalosporins. The present review focuses attention on the problem of stereocontrol in the formation of a Read More

In the last two decades, the better understanding of the mechanistic aspects of the β-lactams' biological activity and their inhibition, and the chemical exploitation of β-lactams as synthetic intermediates in organic chemistry, have experienced a continuous and somewhat complementary advance. A prerequisite for such a development has been the accessibility of enantiopure β-lactams. The latter are now routinely prepar Read More

β-Lactams have recently been identified as potent, highly efficacious cholesterol absorption inhibitors (CAIs). The discovery, SAR, and asymmetric synthesis of this class of hypolipidemic agents are described. Metabolism studies of the first clinical candidate, Sch 48461, led to the identification of a more potent second generation clinical candidate, Sch 58235 (ezetimibe) incorporating key structural elements of the active metabolit Read More

Azetidin-2-one, a four-membered cyclic lactam (β-lactam) skeleton has been recognised as a useful building block for the synthesis of a large number of organic molecules by exploiting the strain energy associated with it, in addition to its use in the synthesis of a variety of β-lactam antibiotics. Efforts have been made in exploring such new aspects of β-lactam chemistry using enantiomerically pure β-lactams as versa Read More

Since the advent of penicillin, the β-lactam antibiotics have been the subject of much discussion and investigation, within both the scientific and public sectors. The primary biological targets of the β-lactam antibacterial drugs are the penicillin binding proteins, a group of transpeptidases anchored within the bacterial cellular membrane, which mediate the final step of cell wall biosynthesis. The extensive use of common β- Read More

While β-lactam antibiotics remain among the most commonly prescribed pharmaceutical products, their effectiveness is currently threatened by the development of bacterial resistance. One key resistance mechanism is the ability to destroy the antibiotic through utilization of one or more types of β-lactamase. An effective countermeasure is to employ a combination product, consisting of both a β-lactam antibiotic and a β- Read More