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-β-lactamases (MBLs) NDM-1 and VIM-1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity.
Author:Mikhail Krasavin, Daniil Zhukovsky, Igor Solovyev, Darina Barkhatova, Dmitry Dar'in, Denia Frank, Giada Martinelli, Lilia Weizel, Anna Proschak, Marco Rotter, Jan S. Kramer, Steffen Brunst, Thomas Alexander Wichelhaus, Ewgenij ProschakORCiDGND
Parent Title (English):ChemMedChem
Place of publication:Weinheim [u.a.]
Document Type:Article
Date of Publication (online):2021/06/29
Date of first Publication:2021/06/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/04/05
Tag:Rh(II) catalysis; diazo compounds; metallo β lactamases; multiresistant bacteria; thiol inhibitors
Page Number:8
First Page:3410
Last Page:3417
This research was supported by the German Research Foundation and Russian Basic Research Foundation (DFG-RBRF joint research grant PR/1405/8-1; 21-53-12001). E.P. thanks DFG for Heisenberg-Professorship PR1405/7-1. Open Access funding enabled and organized by Projekt DEAL.
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0