β-lactam

Examples of β-lactam in the following topics:

• Beta-Lactam Antibiotics: Penicillins and Cephalosporins

  • The β-lactam ring is part of the core structure of several antibiotic families.
  • A β-lactam (beta-lactam) ring, is a four-membered lactam .
  • The simplest β-lactam possible is 2-azetidinone.
  • 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.
  • Together with cephamycins, they constitute a subgroup of β-lactam antibiotics called cephems.

• Inhibiting Cell Wall Synthesis

  • β-Lactam (beta-lactam) and glycopeptide antibiotics work by inhibiting or interfering with cell wall synthesis of the target bacteria.
  • The first class of antimicrobial drugs that interfere with cell wall synthesis are the β-Lactam antibiotics (beta-lactam antibiotics), consisting of all antibiotic agents that contains a β-lactam nucleus in their molecular structures.
  • PBPs vary in their affinity for binding penicillin or other β-lactam antibiotics.
  • Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring.
  • To overcome this resistance, β-lactam antibiotics are often given with β-lactamase inhibitors such as clavulanic acid.

• Related Carbonyl Derivatives

  • Cyclic esters are called lactones, and cyclic amides are referred to as lactams.
  • Penicillin G has two amide functions, one of which is a β-lactam.

• Naturally Occurring Antimicrobial Drugs: Antibiotics

  • There are mainly two classes of antimicrobial drugs: those obtained from natural sources (i.e. beta-lactam) antibiotic (such as penicillins, cephalosporins) or protein synthesis inhibitors (such as aminoglycosides, macrolides, tetracyclines, chloramphenicol, polypeptides); and synthetic agents.
  • 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.

• Four-Membered Rings

  • Cleavage reactions of β-lactones may take place either by acid-catalyzed acyl exchange, as in 4a, or by alkyl-O rupture by nucleophiles, as in 4b.
  • Finally, the β-lactam cleavage of penicillin G (reaction 6) testifies to the enhanced acylating reactivity of this fused ring system.

• Antibiotic Classifications

  • Examples include the Beta-lactam antibiotics (penicillin derivatives (penams) ), cephalosporins (cephems), monobactams, and carbapenems) and vancomycin.
  • Penicillin and most other β-lactam antibiotics act by inhibiting penicillin-binding proteins, which normally catalyze cross-linking of bacterial cell walls.

• Protein Structure

  • In β-pleated sheets, stretches of amino acids are held in an almost fully-extended conformation that "pleats" or zig-zags due to the non-linear nature of single C-C and C-N covalent bonds. β-pleated sheets never occur alone.
  • They have to held in place by other β-pleated sheets.
  • The stretches of amino acids in β-pleated sheets are held in their pleated sheet structure because hydrogen bonds form between the oxygen atom in a polypeptide backbone carbonyl group of one β-pleated sheet and the hydrogen atom in a polypeptide backbone amino group of another β-pleated sheet.
  • The β-pleated sheets which hold each other together align parallel or antiparallel to each other.
  • The R groups of the amino acids in a β-pleated sheet point out perpendicular to the hydrogen bonds holding the β-pleated sheets together, and are not involved in maintaining the β-pleated sheet structure.

• Diastereoselection in Reactions with Chiral Enolates

  • These Z-enolates are expected to favor 1,2-syn diastereoselectivity of the newly created α & β chiral centers, as noted earlier.
  • Excellent facial selectivity is found in reactions of these nucleophiles Here the 1,2-diastereoselectivity of the newly created α & β chiral centers is strongly anti, as expected.
  • However, the 1,4-diastereoselectivity (α':β) is not consistent.
  • Again, strong facial selectivity is displayed for bonding at the re-face of the enolate as drawn, with both the new 1,2- (α:β) and 1,4- (α':β) diastereoselectivities being syn, as expected.
  • From past observations, the 1,2-diastereoselectivity of the newly created α & β chiral centers is expected to exhibit moderate syn-diastereoselectivity.

• 1:3-Diastereoselection in Reactions with Chiral Aldehydes

  • Two examples of 1:3-diastereoselection in reactions of β-substituted aldehydes are shown in the following diagram.
  • In these cases the influence of the α and β- substituents conflict and are nonreinforcing.
  • Also the known preference of the Mukaiyama aldol for α:β syn products is realized with a de varying from 40% to 90%.
  • As expected, the E-borinates give α:β-anti diastereomers exclusively, and the Z-titanium enolates strongly favor the α:β-syn family of isomers.
  • The facial bias imposed on the aldehyde carbonyl group by a β-polar substituent may be seen in the proportions of diastereomers having 1,3-anti (β:δ-anti) configurations (e.g.

• Lipid Metabolism

  • Biological lipids, which are broken down and utilized though β-oxidation, represent a potent energy source.
  • Although not stated explicitly, the "Organic Acid Metabolism" atom in this module introduces the concept of lipid metabolism by describing the process of fatty acid metabolism through β-oxidation.
  • The metabolic process by which fatty acids and their lipidic derivatives are broken down is called β-oxidation.
  • β-oxidation can be broken down into a series of discrete steps:
  • Oxidation: The initial step of β-oxidation is catalyzed by acyl-CoA dehydrogenase, which oxidizes the fatty acyl-CoA molecule to yield enoyl-CoA.