|
|||||
|
|
RhII-Catalyzed De-symmetrization of Ethane-1,2-dithiol and Propane-1,3-dithiol Yields Metallo-β-lactamase Inhibitors |
|
| Authors: | Prof Mikhail Krasavin Daniil Zhukovsky Igor Solovyev Darina Barkhatova Prof Dmitry Dar'in Denia Frank Giada Martinelli Lilia Weizel Dr Anna Proschak Marco Rotter Dr Jan S Kramer Steffen Brunst Prof Thomas A Wichelhaus Prof Ewgenij Proschak |
| Affiliation: | 1. Institute of Chemistry, Saint Petersburg State University 26 Universitetskii prospect, Peterhof, 198905 Russia;2. Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Paul-Ehrlich-Straße 40, 60596 Frankfurt, Germany;3. Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue Str. 9, 60438 Frankfurt a.M., Germany |
| Abstract: | 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-β-lactamases (MBLs) NDM-1 and VIM-1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity. |
| Keywords: | multiresistant bacteria metallo β lactamases thiol inhibitors Rh(II) catalysis diazo compounds |