A  beta-lactam (β-lactam) ring is a four-membered lactam.
A lactam is a cyclic amide, and beta-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl.
The simplest β-lactam possible is 2-azetidinone.
β-lactams are significant structural units of medicines as manifested in many β-Lactam antibiotics 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.
Clinical significance
thumb|180px|Penicillin core structure 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 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.
Synthesis
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 [2+2] cycloaddition (Ph indicates a phenyl functional group):
Image:StaudingerLactam.svg
Many methods have been developed for the synthesis of β-lactams.
The Breckpot β-lactam synthesis produces substituted β-lactams by the cyclization of beta amino acid esters by use of a Grignard reagent.
Mukaiyama's reagent is also used in modified Breckpot synthesis.
Breckpot synthesis
Reactions
Due to ring strain, β-lactams are more readily hydrolyzed than linear amides or larger lactams.
This strain is further increased by fusion to a second ring, as found in most β-lactam antibiotics.
This trend is due to the amide character of the β-lactam being reduced by the aplanarity of the system.
The nitrogen atom of an ideal amide is sp2-hybridized due to resonance, and sp2-hybridized atoms have trigonal planar bond geometry.
As a pyramidal bond geometry is forced upon the nitrogen atom by the ring strain, the resonance of the amide bond is reduced, and the carbonyl becomes more ketone-like.
Nobel laureate Robert Burns Woodward described a parameter h as a measure of the height of the trigonal pyramid defined by the nitrogen (as the apex) and its three adjacent atoms.
h corresponds to the strength of the β-lactam bond with lower numbers (more planar; more like ideal amides) being stronger and less reactive.
Monobactams have h values between 0.05 and 0.10 angstroms (Å).
Cephems have h values in of 0.20–0.25 Å.
Penams have values in the range 0.40–0.50 Å, while carbapenems and clavams have values of 0.50–0.60 Å, being the most reactive of the β-lactams toward hydrolysis.
See also
Azetidine
Lactone
Lectka enantioselective beta-lactam synthesis
References
External links
Synthesis of β-lactams
