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

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

Automated summary

Here we report a stereoselective synthesis method for the tricyclic beta-lactam core, which is obtained from an accessible and inexpensive commercially available cephalosporin intermediate through sulfoxide-directed oxidative lactonization in six steps, with a total yield of 23%.