Lecture 2 - Beta Lactam Antibiotics

Question 1

Draw a ß-lactam ring.

Answer 1

Question 2

Draw and annotate the structure of the first penicillins.

Answer 2

Question 3

Outline the properties of Penicillin G.

Answer 3

• Active against gram +ve Staphylcocci and many gram -ve cocci.
• Acid sensitive so cannot be taken orally otherwise it is hydrolysed in the stomach.
• Ineffective against bacteria that produce ß-lactamases.
• Mode of action can lead to an allergic reaction.

Question 4

Outline the acid instability of penicillins.

Answer 4

• ß-lactam carbonyl has more ketone character than amide i.e. is more electrophilic.
• Due to the N lone pair not being able to delocalise into the ring:
  
  • No C=N double bond character.
  • Isolated carbonyl is more electrophilic, more reactive + easier to hydrolyse.
• Reactivity further reduced due to poor overlap between N lone pair and the carbonyl.

Question 5

Draw a mechanism for the degradation of pencillin G.

Answer 5

• Intramolecular cyclisation via N lone pair.
• Can alter stability by changing the R group, reducing the nucleophilicity of the carbonyl group → no intramolecular cyclisation.

Question 6

Penicillin V

Answer 6

• First orally active penicillin, produced on a PhOCH₂CO₂H growth medium.
• Electronegativity of O decreases nucleophilicity of adjacent carbonyl → more stable in acidic conditions.