Lactams

In chemistry, a lactam is a cyclic amide. The name is derived from two chemical terms, lactone, referring to a cyclic ketone, and amide, a compound containing a nitrogen atom next to a carbonyl group. Lactams are named according to the size of the cyclic ring in the lactam: α-lactams, β-lactams, γ-lactams and δ-lactams contain rings made of three, four, five or six atoms, respectively. α-lactams are also called aziridinones. Many widely used antibiotic drugs, including the penicillins and cephalosporins, owe their activity to the presence of a β-lactam structure. The lactams may have substitutions added to the nitrogen atom or any of the non-carbonyl carbon atoms in the base structure. 

Synthesis

General synthetic methods exist for the organic synthesis of lactams.

Ø  Lactams form by the acid-catalyzed rearrangement of oximes in the Beckmann rearrangement.

Ø  Lactams form from cyclic ketones and hydrazoic acid in the Schmidt reaction.

Ø  Lactams form from cyclisation of amino acids.

Ø  Lactams form from intramolecular attack of linear acyl derivatives from the nucleophilic abstraction reaction.

Ø  In iodolactamization an iminium ion reacts with an halonium ion formed in situ by reaction of an alkene with iodine.

 

Ø  Lactams form by copper catalyzed 1,3-dipolar cycloaddition of alkynes and nitrones in the Kinugasa reaction

Ø  Diels-Alder reaction between cyclopentadiene and chlorosulfonyl isocyanate (CSI) can be utilized to obtain both β- as well as γ-lactam. At lower temp (−78 °C) β-lactam is the preferred product. At optimum temperatures, a highly useful γ-lactam known as Vince Lactam is obtained.

 

Synthesis of alpha-lactams

The cyclization reaction of an α-haloamide precuror in the presence of sodium hydride and 15-crown-5 ether at room temperature in dichloromethane (CH₂Cl₂) is a high-yielding, general route to α-lactam (aziridinone) products. The hydrogen gas and sodium halide by-products are readily removed.

 

Antibiotics

The β-lactam forms the center structure of many antibiotic drugs, such as the cephalosporins and the penicillins, as shown above. In the penicillins, the non-lactam ring is one atom smaller compared to the cephalosporins. The activity of cephalosporins, penicillins, and some other antibiotics are due to the presence of the beta-lactam, which binds irreversibly, via acylation, to penicillin-binding proteins, thereby inhibiting the peptidogycan layer of bacterial cell wall synthesis. Cephalosporins and penicillins are often made semi-synthetically, using a core structure obtained from a natural organism, such as a fungus, due to the difficulty and expense of synthesizing these lactams.

Beta-lactams are four-membered cyclic amides, best known for the penicillins based on a bicyclo-thiazolidine, as well as the cephalosporins based on a bicyclo-thiazine, and including monocyclic monobactams. The beta-lactamases hydrolyze the beta lactam ring, accounting for beta-lactam resistance of infective bacteria.

 

~~forgiveness if there are mistakes~~