Synthesis of 2‑Thio-Substituted 1,6-Diazabicyclo[3.2.1]octane Derivatives, Potent β‑Lactamase Inhibitors

Approval of avibactam
by the FDA has led to the recognition of
1,6-diazabicyclo[3.2.1]­octane (DBO) derivatives as attractive compounds
for β-lactamase inhibition. We achieved a concise and collective
synthesis of 2-thio-substituted DBO derivatives. The synthesis involves
diastereoselective photo-induced Barton decarboxylative thiolation,
which can be applied to large-scale synthesis. The DBO analogues exhibited
strong inhibitory activities against serine β-lactamases and
acceptable solution stabilities for clinical development.