Question

Early research into the mechanism of antibiotics theorized that it was implausible that the amide in penicillin would convert to an ester. Which of the following explains this doubt?

1) Amides possess better leaving groups than esters.
2) Esters possess poorer leaving groups than amides.
3) Amides are less reactive than esters.
4) Serine contains no good nucleophiles.

Answer 1

Early skepticism about the conversion of penicillin's amide to an ester was due to the lower reactivity of amides compared to esters, reinforced by the vital role of the reactive ß-lactam ring in penicillin's antibacterial action.

Step-by-step explanation:

Early research into the mechanism of antibiotics raised doubts regarding the conversion of the amide in penicillin to an ester. The reason for this doubt can be explained by the fact that amides are less reactive than esters. This is due to the resonance stabilization in amides which makes them poor leaving groups. In comparison, esters have better-leaving groups, allowing for the acyl substitution reactions necessary for ester formation. Penicillin, a renowned ß-lactam antibiotic, contains a strained ß-lactam ring that is crucial for its antibacterial activity. It mimics the substrate of the transpeptidase enzyme and irreversibly inhibits it, preventing the synthesis of bacterial cell walls. This mechanism highlights the importance of penicillin's reactivity and underpins the skepticism early researchers had about its transformation into an ester.