ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
ACS_ML_V2.pdf (10.88 MB)

Semisynthetic Analogs of the Antibiotic Fidaxomicin – Design, Synthesis, and Biological Evaluation

preprint
submitted on 06.07.2020 and posted on 07.07.2020 by Andrea Dorst, Regina Berg, Christoph Gertzen, Daniel Schäfle, katja zerbe, myriam gwerder, Simon Schnell, Peter Sander, Holger Gohlke, Karl Gademann

The glycoslated macrocyclic antibiotic fidaxomicin (1, tiacumicin B, lipiarmycin A3) displays good to excellent activity against Gram-positive bacteria and was approved for the treatment of Clostridium difficile infections (CDI). Main limitations of the compound include low water solubility, which impacts further clinical use. We report on the synthesis of new fidaxomicin derivatives based on structural design and utilizing an operationally simple one-step protecting group-free preparative approach from the natural product. An increase in solubility of up to 25-fold with largely retained activity was observed. Furthermore, hybrid antibiotics were prepared that show improved antibiotic activities

Funding

Swiss National Science Foundation (200021_182043 (K.G.) and 31003A_153349/1 (P.S.)) Swiss Lung Association (2018-02). DFG (GRK 2158, P4 for H.G.)

History

Email Address of Submitting Author

karl.gademann@uzh.ch

Institution

University of Zurich

Country

Switzerland

ORCID For Submitting Author

0000-0003-3053-0689

Declaration of Conflict of Interest

None

Exports