Strong nucleophiles will also open the strained ether, as shown by reaction 3b. Cleavage reactions of β-lactones may take place either by acid-catalyzed acyl exchange, as in 4a, or by alkyl-O rupture by nucleophiles, as in 4b. Example 5 is an interesting case of intramolecular rearrangement to an ortho-ester. Finally, the β-lactam cleavage of penicillin G (reaction 6) testifies to the enhanced acylating reactivity of this fused ring system. Most amides are extremely unreactive acylation reagents, thanks to stabilization by p-π resonance. Such electron pair delocalization is diminished in the penicillins, leaving the nitrogen with a pyramidal configuration and the carbonyl function more reactive toward nucleophiles.