Synthesis of pyrrolidine‐fused β‐lactams as potential β‐lactamase inhibitors

A synthetic protocol for the preparation of novel 3,4‐pyrrolidine‐fused β‐lactams was developed. The proposed 2,6‐diazabicyclo[3.2.0]heptan‐7‐one scaffolds were constructed through an amido group‐induced, potassium tert ‐butoxide‐promoted intramolecular ring closure of 3‐acylamino‐4‐oxiranyl‐β‐lactams as the key reaction step. Alternatively, the desired cyclization was also effected by means of a scandium triflate‐mediated catalytic approach. In this way, a set of stereodefined 3,4‐pyrrolidine‐fused β‐lactams was synthesized, which were preliminary evaluated as β‐lactamase inhibitors. These first‐line biological assessments led to the identification of a 2‐benzoyl‐6‐(4‐methoxyphenyl)‐substituted diazabicyclo structure as an eligible starting point for further β‐lactamase inhibitor optimization studies.