Kamis, 07 Juni 2012

β-lactam


β-lactam (beta-lactam)
A.  Defenition

A β-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 β-carbon relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone.

 
B.  Clinical significance
              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. Bacteria do, however contain within their populations, in smaller quantities, bacteria that are resistant against β-lactam antibiotics. They do this by by expressing the β-lactamase gene. When bacterial populations have these resistant subgroups, treatment with β-lactam can result in the resistant strain becoming more prevelant and so more virulent.

C.  History
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:






D.     Nomenclature
 The β-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.

*        β-Lactams are classified according to their core ring structures.
·       β-Lactams fused to saturated five-membered rings:
o   β-Lactams containing thiazolidine rings are named penams.
o   β-Lactams containing pyrrolidine rings are named carbapenams.
o   β-Lactams fused to oxazolidine rings are named oxapenams or clavams.
·       β-Lactams fused to unsaturated five-membered rings:
o    β-Lactams containing 2,3-dihydrothiazole rings are named penems.
o   β-Lactams containing 2,3-dihydro-1H-pyrrole rings are named carbapenems.
·       β-Lactams fused to unsaturated six-membered rings:
o   β-Lactams containing 3,6-dihydro-2H-1,3-thiazine rings are named cephems.
o   β-Lactams containing 1,2,3,4-tetrahydropyridine rings are named carbacephems.
o   β-Lactams containing 3,6-dihydro-2H-1,3-oxazine rings are named oxacephems.
·       β-Lactams not fused to any other ring are named monobactams.
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.

E.     Reactivity
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. 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. 

F.    New application
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.

2 komentar:

  1. Pauline
    How the δ-lactam, lactam Ύ ..??
    please your opinion ^_^

    BalasHapus
    Balasan
    1. thx before olin..
      ok, i will try to answer

      we kow that the lactam defided of a β-lactam, a γ-lactam, a δ-lactam and a ε-lactam. actually γ-lactam is inckude of lactam .its just called to essy for us to used and able to different the kind of lactam.

      A cyclic amide that is the nitrogen analog of a lactone. For example, a γ-aminobutyric acid readily forms γ-butyrolactam (also known as 2-pyrrolidinone) upon heating, as in the reaction below. The tautomeric enol form of a lactam is known as a lactim.

      Hapus