| β-Lactam | |
|---|---|
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2-Azetidinone |
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| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) | |
| Infobox references |
A β-lactam (beta-lactam) ring, is a four-membered lactam.[1] (A lactam is a cyclic amide.) It is named as such, because the nitrogen atom is attached to the β-carbon relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone.
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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. Bacteria can, however, become resistant against β-lactam antibiotics by expressing a β-lactamase.
The first synthetic β-lactam was prepared by Hermann Staudinger in 1907 by reaction of the Schiff base of aniline and benzaldehyde with diphenylketene[2][3] in a [2+2]cycloaddition:
β-Lactams are classified according to their core ring structures.[4]
By convention, the bicyclic β-lactams are numbered starting with the position occupied by sulfur in the penams and cephems, regardless of which atom it is in a given class. That is, position 1 is always adjacent to the β-carbon of β-lactam ring. The The numbering continues clockwise from position one until the β-carbon of β-lactam is reached, at which point numbering continues counterclockwise around the lactam ring to number the remaining to carbons. For example, the nitrogen atom of all bicyclic β-lactams fused to five-membered rings is labelled position 4, as it is in penams, while in cephems, the nitrogen is position 5.
The numbering of monobactams follows that of the IUPAC; the nitrogen atom is position 1, the carbonyl carbon is 2, the α-carbon is 3, and the β-carbon 4.
Due to ring strain, β-lactams are more reactive to hydrolysis conditions than are 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 amid bond is reduced, and the carbonyl becomes more ketone-like. Nobel laureate 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.[5] 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 crabapenems and clavams have values of 0.50–0.60 Å, being the most reactive of the β-lactams toward hydrolysis.[6]
A new study has suggested that β-lactams can undergo ring-openening polymerization to form amide bonds, to become nylon-3 polymers. The backbones of these polymers are identical to peptides, which offer them biofunctionality. A recent study has showed that these nylon-3 polymers can either mimic host defense peptides or act as signals to stimulate 3T3 stem cell function.