The -Lactam Antibiotics and Penicillin

The -Lactam Antibiotics

• The largest group of antibiotics, comprising around 60% of all antibiotics.
• Characterized by containing a -lactam group, which is a cyclic amide.
• The nitrogen atom in the -lactam group is neutral in reactions because its lone pair of electrons is involved in delocalization.

Penicillin

• Penicillin F is highly effective against Gram-positive bacteria like S.aureus and is very safe.
• Despite its effectiveness, it is expensive due to low yields.
• Penicillin G, derived from phenylacetic acid, is cheaper and has the same activity and safety as Penicillin F.
• Penicillin G is produced using corn steep liquor as a media, which is rich in phenylacetic acid.
• Penicillin F, on the other hand, is produced using a defined media containing sucrose, vitamin B1, and C6 fatty acid.
• Penicillin G is the only natural penicillin in use.

Acid Stability and Intramolecular Reactions in Penicillin

• Penicillin G is unstable in acidic environments due to its susceptibility to hydrolysis, forming benzylpenicilloic acid.
• Hydrolysis occurs through both intermolecular and intramolecular reactions.
• Intramolecular hydrolysis, where the amide side chain attacks the -lactam carbonyl group, is the more efficient pathway.
• The amide side chain's ability to effectively act as a nucleophile is influenced by electron withdrawing groups that decrease its electron density.

Designing Acid-Stable Penicillin Derivatives

• To design an orally active (acid-stable) penicillin, the intramolecular reaction must be minimized by modifying the amide side chain.
• The side chain should contain an electron withdrawing group to reduce its nucleophilicity.
• The side chain needs to be rigidly fixed to prevent rotation and squeezing, ensuring it doesn't fit into the active site and undergo hydrolysis.

Methicillin: Penicillinase-Resistant

• Methicillin is a penicillinase-resistant derivative, achieved by incorporating methoxy groups (OCH3) into its structure.
• Methoxy groups are electron donating groups, making methicillin acid-unstable and unsuitable for oral administration.

Isoxazole PRP and Oxacillin

• Isoxazole PRP penicillin derivatives are eliminated via renal and hepatic routes.
• Oxacillin, an orally active isoxazole PRP, gets its acid stability from the nitrogen atom in the isoxazole ring having some basicity.

Explore the fascinating world of -lactam antibiotics, with a focus on Penicillin. Learn about its effectiveness against Gram-positive bacteria, production methods, and acid stability issues. This quiz will enhance your understanding of antibiotic mechanisms and classifications.