RhII-Catalyzed De-symmetrization of Ethane-1,2-dithiol and Propane-1,3-dithiol Yields Metallo-β-lactamase Inhibitors

Diversity-oriented synthesis (DOS) is a rich source for novel lead structures in Medicinal Chemistry. In this study, we present a DOS-compatible method for synthesis of compounds bearing a free thiol moiety. The procedure relies on Rh(II)-catalyzed coupling of dithiols to diazo building blocks. The synthetized library was probed against metallo-beta-lactamases (MBLs) NDM-1 and VIM-1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity.

Automated summary

Diversity-oriented synthesis is a valuable approach for discovering novel drug lead structures in Medicinal Chemistry. This study describes a DOS-compatible method for synthesizing compounds with a free thiol moiety, leading to the identification of novel potent MBL inhibitors with antibiotic adjuvant activity through biochemical and biological evaluation.