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Rh II ‐Catalyzed De‐symmetrization of Ethane‐1,2‐dithiol and Propane‐1,3‐dithiol Yields Metallo‐β‐lactamase Inhibitors
Author(s) -
Krasavin Mikhail,
Zhukovsky Daniil,
Solovyev Igor,
Barkhatova Darina,
Dar'in Dmitry,
Frank Denia,
Martinelli Giada,
Weizel Lilia,
Proschak Anna,
Rotter Marco,
Kramer Jan S.,
Brunst Steffen,
Wichelhaus Thomas A.,
Proschak Ewgenij
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100344
Subject(s) - dithiol , chemistry , moiety , diazo , thiol , catalysis , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry
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.