A
β-lactam ring, is a four-membered
lactamA lactam is a cyclic amide. Prefixes indicate how many carbon atoms are present in the ring: β-lactam , γ-lactam , δ-lactam...
. (A lactam is a cyclic
amideIn chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
.) 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.
Clinical significance
The β-lactam ring is part of the core structure of several
antibioticAn antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
families, the principal ones being the
penicillinPenicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
s,
cephalosporinThe cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
s,
carbapenemCarbapenems are a class of β-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to most β-lactamases...
s, and monobactams, which are, therefore, also called
β-lactam antibioticβ-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam nucleus in its molecular structure. This includes penicillin derivatives , cephalosporins , monobactams, and carbapenems...
s. Nearly all of these antibiotics work by inhibiting bacterial
cell wallThe cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...
biosynthesis. This has a lethal effect on
bacteriaBacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. Bacteria can, however, become
resistantAntibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
against β-lactam antibiotics by expressing a
β-lactamaseBeta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
.
History
The first synthetic β-lactam was prepared by
Hermann Staudinger- External links :* Staudinger's * Staudinger's Nobel Lecture *....
in 1907 by reaction of the
Schiff baseA Schiff base, named after Hugo Schiff, is a compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group, not hydrogen....
of
anilineAniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane...
and
benzaldehydeBenzaldehyde is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. This colorless liquid has a characteristic pleasant almond-like odor...
with
diphenylketeneDiphenylketene is a chemical of the ketene family. Diphenylketene, like most disubstituted ketenes is a red/orange oil at room temperature and pressure.-Chemistry and reactivity:...
in a [2+2]
cycloadditionA cycloaddition is a pericyclic chemical reaction, in which "two or more unsaturated molecules combine with the formation of a cyclic adduct in which there is a net reduction of the bond multiplicity." The resulting reaction is a cyclization reaction.Cycloadditions are usually described by the...
:
Reactivity
Due to
ring strainIn organic chemistry, ring strain is the tendency of a cyclic molecule, such as cyclopropane, to destabilize when its atoms are in non-favorable high energy spatial orientations...
, β-lactams are far more reactive to
hydrolysisHydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
conditions than are linear
amideIn chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
s or larger
lactamA lactam is a cyclic amide. Prefixes indicate how many carbon atoms are present in the ring: β-lactam , γ-lactam , δ-lactam...
s. This strain is further increased by fusion to a second ring, as found in most β-lactam antibiotics.
Nomenclature
β-Lactams are classified according to their core ring structures.
- β-Lactams fused to saturated
In chemistry, saturation has six different meanings, all based on reaching a maximum capacity...
five-membered rings:
- β-Lactams containing thiazolidine
Thiazolidines are a class of heterocyclic organic compounds with a 5-membered saturated ring with a thioether group and an amine group in the 1 and 3 positions, respectively. It is a sulfur analogue of oxazolidine. The drug pioglitazone contains a thiazolidine ring. It is a drug usually indicated...
rings are named penamPenams are a subclass of the broader β-lactam family of antibiotics and related compounds. Penams contain a β-lactam ring fused to a 5-membered ring, where one of the atoms in the ring is a sulfur and the ring is fully saturated. Penicillin is a member of this family of compounds....
s.
- β-Lactams containing pyrrolidine
Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula C4H9N. It is a cyclic secondary amine with a five-membered heterocycle containing four carbon atoms and one nitrogen atom...
rings are named carbapenamA carbapenam is a β-lactam compound that is a saturated carbapenem. They exist primarily as biosynthetic intermediates on the way to the carbapenem antibiotics....
s.
- β-Lactams fused to oxazolidine
Oxazolidine is a five-membered ring compound consisting of three carbons, a nitrogen, a hydrogen, and an oxygen. The oxygen and NH are the 1 and 3 positions, respectively. In oxazolidine derivatives, there is always a carbon between the oxygen and the nitrogen . All of the carbons in oxazolidines...
rings are named oxapenams or clavamA clavam is a molecule similar to a penam, but with an oxygen substituted for the sulfur. Thus, they are also known as oxapenams.An example is clavulanic acid....
s.
- β-Lactams fused to unsaturated five-membered rings:
- β-Lactams containing 2,3-dihydrothiazole
Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen; the term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular formula C3H3NS...
rings are named penemA penem is a type of unsaturated β-lactam.An example is faropenem.Penems are similar in structure to carbapenems. However, where penems have a sulfur, carbapenems have another carbon....
s.
- β-Lactams containing 2,3-dihydro-1H-pyrrole
Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH. It is a colourless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3...
rings are named carbapenemCarbapenems are a class of β-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to most β-lactamases...
s.
- β-Lactams fused to unsaturated six-membered rings:
- β-Lactams containing 3,6-dihydro-2H-1,3-thiazine
Thiazines are organic compounds containing a ring of four carbon, one nitrogen and one sulfur atom. Chemicals that include thiazine are used for dyes, tranquilizers and insecticides.-See also:*Methylene blue*Phenothiazine*Heterocyclic compound*Morpholine...
rings are named cephemCephems are a sub-group of beta-lactam antibiotics including cephalosporins and cephamycins....
s.
- β-Lactams containing 1,2,3,4-tetrahydropyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
rings are named carbacephemA carbacephem is a type of synthetically made antibiotic, based on the structure of cephalosporin, a cephem. Carbacephems are similar to cephems but with a carbon substituted for the sulfur....
s.
- β-Lactams containing 3,6-dihydro-2H-1,3-oxazine rings are named oxacephem
An oxacephem is a molecule similar to a cephem, but with oxygen substituted for the sulfur. They are synthetically made compounds and have not been discovered in nature.An example is moxalactam.Another example is flomoxef....
s.
- β-Lactams not fused to any other ring are named monobactams.
New application
A new study has suggested that β-lactams can undergo ring-openening
polymerizationIn polymer chemistry, polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains...
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 cellThis article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
function.
See also
- Azetidine
Azetidine is a heterocyclic organic compound. It belongs to the class of four membered rings and it contains a nitrogen atom.-External links:* *...
- Lactam
A lactam is a cyclic amide. Prefixes indicate how many carbon atoms are present in the ring: β-lactam , γ-lactam , δ-lactam...
- Lactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
- β-lactam antibiotics
External links