TY  - JOUR
AU  - Dorst, Andrea
AU  - Berg, Regina
AU  - Gertzen, Christoph G. W.
AU  - Schäfle, Daniel
AU  - Zerbe, Katja
AU  - Gwerder, Myriam
AU  - Schnell, Simon D.
AU  - Sander, Peter
AU  - Gohlke, Holger
AU  - Gademann, Karl
TI  - Semisynthetic Analogs of the Antibiotic Fidaxomicin—Design, Synthesis, and Biological Evaluation
JO  - ACS medicinal chemistry letters
VL  - 11
IS  - 12
SN  - 1948-5875
CY  - Washington, DC
PB  - ACS
M1  - FZJ-2020-04094
SP  - 2414–2420
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 33329763
UR  - <Go to ISI:>//WOS:000599586900006
DO  - DOI:10.1021/acsmedchemlett.0c00381
UR  - https://juser.fz-juelich.de/record/885797
ER  -