Beta-lactam

A beta-lactam (β-lactam) ring is a four-membered lactam. (A lactam is a cyclic amide.) It is named as such because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone. A beta-lactam (β-lactam) ring is a four-membered lactam. (A lactam is a cyclic amide.) It is named as such because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone. The β-lactam ring is part of the core structure of several antibiotic families, the principal ones being the penicillins, cephalosporins, carbapenems, and monobactams, which are, therefore, also called β-lactam antibiotics. Nearly all of these antibiotics work by inhibiting bacterial cell wall biosynthesis. This has a lethal effect on bacteria, although any given bacteria population will typically contain a subgroup that is resistant to β-lactam antibiotics. Bacterial resistance occurs as a result of the expression of one of many genes for the production of β-lactamases, a class of enzymes that break open the β-lactam ring. More than 1,800 different β-lactamase enzymes have been documented in various species of bacteria. These enzymes vary widely in their chemical structure and catalytic efficiencies. When bacterial populations have these resistant subgroups, treatment with β-lactam can result in the resistant strain becoming more prevalent and therefore more virulent. β-lactam derived antibiotics can be considered as one of the most important antibiotic classes but prone to clinical resistance. β-lactam exhibits its antibiotic properties by imitating the naturally occurring d-Ala-d-Ala substrate for the group of enzymes known as penicillin-binding proteins (PBP), which have as function to cross-link the peptidoglycan part of the cell wall of the bacteria. The first synthetic β-lactam was prepared by Hermann Staudinger in 1907 by reaction of the Schiff base of aniline and benzaldehyde with diphenylketene in a cycloaddition (Ph indicates a phenyl functional group): Up to 1970, most β-lactam research was concerned with the penicillin and cephalosporin groups, but since then, a wide variety of structures have been described.