Dataset for "Phenolic Substitution in Fidaxomicin: A Semisynthetic Approach to Antibiotic Activity Across Species"

<p>ZIP File:</p> <p>Characterisation data (such as e.g. NMR, IR, MS spectra)</p> <p>NMR raw data, .mnova files</p> <p>ChemDraw drawings (.cdx files)</p> <p>PDF file:</p> <p>Supporting information for</p> <p><strong>Phenolic Substitution in Fidaxomicin: A Semisynthetic Approach to Antibiotic Activity Across Species</strong></p> <p><br> Erik Jung,[a] Anastassia Kraimps,[a] Silvia Dittmann,[b] Tizian Griesser,[c] Jordan Costafrolaz,[d] Yves Mattenberger,[d] Simon Jurt,[a] Patrick H. Viollier,[d] Peter Sander,[c] Susanne Sievers,[b] and Karl Gademann*[a]</p> <p>[a] E. Jung, A. Kraimps, S. Jurt, Prof. Dr. K. Gademann Department of Chemistry, University of Zurich 8057 Z&uuml;rich (Switzerland)<br> E-mail: karl.gademann@uzh.ch<br> [b] S. Dittmann, Dr. S. Sievers<br> Department of Microbial Physiology and Molecular Biology Institute of Microbiology<br> Center for Functional Genomics of Microbes<br> University of Greifswald<br> Greifswald (Germany)<br> [c] T. Griesser, Prof. Dr. P. Sander Institute of Medical Microbiology University of Zurich<br> Zurich (Switzerland)<br> [d] J. Costafrolaz, Dr. Y. Mattenberger, Prof. Dr. P. H. Viollier Department of Microbiology and Molecular Medicine Faculty of Medicine, University of Geneva<br> Geneva (Switzerland)<br> &nbsp;</p> <p>Abstract of the corresponding publication:</p> <p>Fidaxomicin (Fdx) is a natural product antibiotic with potent activity against Clostridioides difficile and other Gram-positive bacteria such as Mycobacterium tuberculosis. Only a few Fdx derivatives have been synthesized and examined for their biological activity in the 50 years since its discovery. Fdx has a well-studied mechanism of action, namely inhibition of the bacterial RNA polymerase. Yet, the targeted organisms harbor different target protein sequences, which poses a challenge for the rational development of new semisynthetic Fdx derivatives. We introduced substituents on the two phenolic hydroxy<br> groups of Fdx and evaluated the resulting trends in antibiotic activity against M. tuberculosis, C. difficile, and the Gram-neg- ative model organism Caulobacter crescentus. As suggested by the target protein structures, we identified the preferable derivatisation site for each organism. The derivative ortho- methyl Fdx also exhibited activity against the Gram-negative C. crescentus wild type, a first for fidaxomicin antibiotics. These insights will guide the synthesis of next-generation fidaxomicin antibiotics.</p>