Stereoselective Synthesis of Tricyclic β-Lactam by Sulfoxide-Directed Oxidative Lactonization from an Accessible
Jun Sato1, Takuya Oguma1, Kenji Yamawaki1
1Laboratory for Medicinal Chemistry Research, Shionogi Pharmaceutical Research Center, 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
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.
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