Lactam

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: -lactams, -lactams, -lactams and -lactams contain rings made of three, four, five or six atoms, respectively. 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: -lactams are also called aziridinones. Many widely used antibiotic drugs, including the penicillins and cephalosporins, owe their activity to the presence of a -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 of lactams 

General synthetic methods exist for the organic synthesis of lactams.

• Lactams form by the acid-catalyzed rearrangement of oximes in the Beckmann rearrangement.
• Lactams form from cyclic ketones and hydrazoic acid in the Schmidt reaction.
• Lactams form from cyclisation of amino acids.
• Lactams form from intramolecular attack of linear acyl derivatives from the nucleophilic abstraction reaction.
• In iodolactamization  an iminium ion reacts with an halonium ion formed in situ by reaction of an alkene with iodine.

• Lactams form by copper catalyzed 1,3-dipolar cycloaddition of alkynes and nitrones in the Kinugasa reaction
• 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 -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 -lactam (aziridinone) products. The hydrogen gas and sodium halide by-products are readily removed.

Antibiotics

The -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.

Penicillin

Penicillin is a wonder drug that saved many lives sicne it was discovered by Alexander Flemming by accident. It was the first antibiotic used in treating bacterial infections and was used in the second worldwar extensively that saved many soldiers lives. It is used today to treat bacterial infections such as ear infections and is the antibiotic of choice in treating infections caused by grampositive bacteria. Penicillins belongs to the ß-lactam antibiotics which are a group of drugs with a central nucleus of ß-lactam in the molecular structure of the drug. ß-lactam antibiotics mode of operation is, inhibiting bacteria from sythesizing the cell wall which kills the bacteria and thus treats the infection. Cephalosporins along with penicillins come under this

What is Penicillin?

Penicillin is group of antibiotics derives from Penicillin fungi. All penicillins are beta-lactam antibiotics and are used in the treatment of bacterial infections caused by mostly gram-positive, organisms.Beta-lactams work by inhibiting the bacteria's ability to synthesize cell wall. Bacteria are smart! In response to this they develop a betalactam synthetase, which actually attacks the beta-lactam ring. Therefore beta- lactam synthetase inhibitor(clavulinic acid) is normally given along with beta lactam antibiotics. It is a secondary metabolite which is produced to stress caused by inhibition of growth of the penicillin fungi.

α-ketoglutarate + AcCoA → homocitrate → L-α-aminoadipic acid → L-Lysine + β-lactam

Penicillin is grown by the fed-batch culture where it is subjected to constant stress resulting in plentiful production of penicillin. The type of substrate used is important. Using glucose inhibits the growth of penicillin but lactose aids in its production. pH of the solution, levels of lysine , oxygen, nitrogen and phosphates must be monitored.

 
What are the indications of Penicillin?

• Treat ear, nose and throat infections
• Respiratory and urinary tract infections
• Prostate infections
• Certain Sexually transmitted diseases
• Skin and soft tissue infections

What are the Side-affects of Penicillin?

• Anaphylaxis, which is a severe allergic reaction that can cause
• skin rash, hives, itching, difficulty breathing, shock, and unconsciousness.
• Warning sign of anaphylaxis is a feeling of warmth and flushing.
• If this occurs, the medicine should be stopped and emergency help sought immediately.

 What are the inventions that  led to the discovery of Penicillin?

• blue mold
• betalactam antibiotics
• grampostive bacteria