Stereoselective Synthesis of Tricyclic β-Lactam by Sulfoxide-Directed Oxidative Lactonization from an Accessible Cephalosporin Intermediate.

Abstract

Tricyclic β-lactam antibiotics show significant antibacterial activities against carbapenem-resistant Enterobacterales (CREs), but the synthesis of a key intermediate for tricyclic β-lactam antibiotics requires eight steps from penicillin with a low total yield of 3% via non-stereoselective lactone formation. Here we report the stereoselective synthesis of the tricyclic β-lactam core by sulfoxide-directed oxidative lactonization from an accessible and inexpensive commercially available cephalosporin intermediate in 23% total yield in six steps.