Carbapenem Antibiotics: Recent Update on Synthesis and Pharmacological Activities

Area of Science:

• Medicinal Chemistry
• Microbiology
• Organic Synthesis

Background:

• Carbapenems represent a critical class of antibiotics, with significant development since their 1976 breakthrough.
• Numerous carbapenem agents have been developed for both parenteral and oral administration, alongside prodrugs enhancing bioavailability.

Approach:

• This review synthesizes information on carbapenem synthesis, structure-activity relationships (SAR), and biological activities.
• It covers various synthetic methodologies, including Witting and Mitsunobu reactions, palladium-catalyzed hydrogenolysis, and E. coli-based cloned synthesis.
• Biosynthetic enzymes like carbapenem synthetase (carA), carboxymethylproline synthase (carB), and carbapenem synthase (carC) are also discussed.

Key Points:

• Parenterally active carbapenems include imipenem, meropenem, and doripenem.
• Orally active carbapenems and prodrugs with enhanced bioavailability are also detailed.
• Carbapenems exhibit broad-spectrum activity against Gram-positive, Gram-negative, and anaerobic bacteria.

Conclusions:

• Carbapenems are vital in treating serious infections such as urinary tract infections, bloodstream infections, tuberculosis, and intra-abdominal infections.
• Their efficacy extends to a wide range of pathogens, underscoring their importance in modern medicine.