-Lactam

1
-Lactam
This article is about the chemical compound. For the related antibiotics, see beta-lactam antibiotic.
-Lactam
Identifiers
CAS number
930-21-2
[1]
PubChem
136721
[2]
ChemSpider
120480
[3]
Jmol-3D images
Image 1
[4]
Properties
Molecular formula C
3
H
5
NO
Molar mass
71.08 g mol
1
Except where noted otherwise, data are given for materials in their standard state (at 25C (77F), 100kPa)
Infoboxreferences
A -lactam (beta-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 -carbon relative to the carbonyl. The simplest -lactam possible is
2-azetidinone.
Clinical significance
Penicillin core structure.
The -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
-Lactam antibiotics. Nearly all of these antibiotics work by inhibiting
bacterial cell wall biosynthesis. This has a lethal effect on bacteria.
Bacteria do, however, contain within their populations, in smaller
quantities, bacteria that are resistant against -lactam antibiotics. They
do this by expressing one of many -lactamase genes. More than 1,000
different -lactamase enzymes have been documented in various
species of bacteria.
[5]
These enzymes vary widely in their chemical structure and catalytic efficiencies. When
bacterial populations have these resistant subgroups, treatment with -lactam can result in the resistant strain
becoming more prevalent and therefore more virulent.
-Lactam
2
History
The first synthetic -lactam was prepared by Hermann Staudinger in 1907 by reaction of the Schiff base of aniline
and benzaldehyde with diphenylketene
[6]
in a [2+2]cycloaddition:
Up to 1970, most -lactam research was concerned with the penicillin and cephalosporin groups, but since then a
wide variety of structures have been described.
Nomenclature
The -lactam core structures. (A) A penam. (B) A carbapenam. (C) An oxapenam.
(D) A penem. (E) A carbapenem. (F) A monobactam. (G) A cephem. (H) A
carbacephem. (I) An oxacephem.
-Lactams are classified according to their
core ring structures.
-Lactams fused to saturated
five-membered rings:
-Lactams containing thiazolidine
rings are named penams.
-Lactams containing pyrrolidine
rings are named carbapenams.
-Lactams fused to oxazolidine rings
are named oxapenams or clavams.
-Lactams fused to unsaturated
five-membered rings:
-Lactams containing
2,3-dihydrothiazole rings are named
penems.
-Lactams containing
2,3-dihydro-1H-pyrrole rings are
named carbapenems.
-Lactams fused to unsaturated
six-membered rings:
-Lactams containing 3,6-dihydro-2H-1,3-thiazine rings are named cephems.
-Lactams containing 1,2,3,4-tetrahydropyridine rings are named carbacephems.
-Lactams containing 3,6-dihydro-2H-1,3-oxazine rings are named oxacephems.
-Lactams not fused to any other ring are named monobactams.
By convention, the bicyclic -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 -carbon of
-lactam ring. The numbering continues clockwise from position one until the -carbon of -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 -lactams fused to five-membered rings is labelled position 4, as it is in
penams, while in cephems, the nitrogen is position 5.
-Lactam
3
The numbering of monolactams follows that of the IUPAC; the nitrogen atom is position 1, the carbonyl carbon is 2,
the -carbon is 3, and the -carbon 4.
Reactivity
Due to ring strain, -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 -lactam antibiotics. This trend is due to the
amide character of the -lactam being reduced by the aplanarity of the system. The nitrogen atom of an ideal amide
is sp
2
-hybridized due to resonance, and sp
2
-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 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 -lactam bond with lower numbers (more planar; more like ideal amides) being stronger and less
reactive.
[7]
Monobactams have h values between 0.05 and 0.10 angstroms (). Cephems have h values in of
0.200.25 . Penams have values in the range 0.400.50 , while carbapenems and clavams have values of
0.500.60 , being the most reactive of the -lactams toward hydrolysis.
[8]
Other applications
A new study has suggested that -lactams can undergo ring-opening 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.Wikipedia:Citation needed
Antiproliferative agents that target tubulin with -lactams in their structure have also been reported.
References
[1] http:/ / www. commonchemistry.org/ ChemicalDetail.aspx?ref=930-21-2
[2] http:/ / pubchem. ncbi. nlm.nih. gov/ summary/ summary. cgi?cid=136721
[3] http:/ / www. chemspider.com/ Chemical-Structure.120480. html
[4] http:/ / chemapps.stolaf. edu/ jmol/ jmol.php?model=C1CNC1%3DO
[5] [5] Ehmann, David E. et al. (2012). "Avibactam is a covalent, reversible, non--lactam -lactamase inhibitor." PNAS. 109(29):11663-11668.
[6] H. Staudinger, Justus Liebigs Ann. Chem. 1907, 356, 51 123.
[7] Woodward, R.B. (1980) "Penems and related substances." Phil Trans Royal Soc Chem B 289(1036), 23950.
[8] Nangia, A.; Biradha, K.; Desiraju, G.R. (1996) "Correlation of biological activity in -lactam antibiotics with Woodward and Cohen
structural parameters: A Cambridge database study." J Chem Soc, Perkin Trans 2 (5), 94353.
External links
Synthesis of -lactams (http:/ / www. organic-chemistry. org/ synthesis/ heterocycles/ lactams/ beta-lactams.
shtm)
Article Sources and Contributors
4
Article Sources and Contributors
-Lactam Source: http://en.wikipedia.org/w/index.php?oldid=610639018 Contributors: 2004-12-29T22:45Z, Admrboltz, Agankrishna, Anypodetos, Arcadian, AtomicDragon, Bemoeial,
Beta-lactam ring records, Calmer Waters, ChrisGualtieri, Conversion script, DARTH SIDIOUS 2, Daniblanco, Dartelaar, Dcirovic, Drphilharmonic, Edgar181, Eionm, Eleassar777, Eras-mus,
Everyking, Frietjes, Gerv, Guy Harris, Heqs, Hstoddard, J1812, JaGa, Jschnur, Kupirijo, Lectonar, Lhynard, LilHelpa, Logan, Magnus Manske, Martastic, Medical Woman, Meiskam, Michael
Hardy, Mirydian, Mysid, Natalya, Newportm, Noisy, Orenburg1, Paul D. Anderson, Peak, Rich Farmbrough, Rod57, SchreiberBike, Shureg, Sugarskane, Techelf, Th84, The sunder king,
Timmy12, Tobias Hoevekamp, Ttony21, V8rik, Whoop whoop pull up, Wikijens, Xchen57, Yikrazuul, , , 72 anonymous edits
Image Sources, Licenses and Contributors
File:Beta-lactam.svg Source: http://en.wikipedia.org/w/index.php?title=File:Beta-lactam.svg License: Public Domain Contributors: Lhynard at en.wikipedia
Image:Penicillin core.svg Source: http://en.wikipedia.org/w/index.php?title=File:Penicillin_core.svg License: Public Domain Contributors: Yikrazuul
Image:StaudingerLactam.svg Source: http://en.wikipedia.org/w/index.php?title=File:StaudingerLactam.svg License: GNU Free Documentation License Contributors: Original uploader was
V8rik at en.wikipedia
Image:Beta-lactam core structures.svg Source: http://en.wikipedia.org/w/index.php?title=File:Beta-lactam_core_structures.svg License: Public Domain Contributors: Fvasconcellos
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