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

ABSTRACT: 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). Among the main limitations for this compound, its low water solubility impacts further clinical uses. 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.

SUBMITTER: Dorst A

PROVIDER: S-EPMC7734799 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Dorst Andrea A Berg Regina R Gertzen Christoph G W CGW Schäfle Daniel D Zerbe Katja K Gwerder Myriam M Schnell Simon D SD Sander Peter P Gohlke Holger H Gademann Karl K

ACS medicinal chemistry letters 20201014 12

The glycoslated macrocyclic antibiotic fidaxomicin (<b>1</b>, tiacumicin B, lipiarmycin A3) displays good to excellent activity against Gram-positive bacteria and was approved for the treatment of <i>Clostridium difficile</i> infections (CDI). Among the main limitations for this compound, its low water solubility impacts further clinical uses. We report on the synthesis of new fidaxomicin derivatives based on structural design and utilizing an operationally simple one-step protecting group-free ...[more]

PMID: 33329763

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