Journal article

Publication year: 2022

Pages: e202100644-

Journal: ChemMedChem

Volume number: 17

Issue number: 6

ISSN: 1860-7179

Open access status: Hybrid

DOI Link: https://doi.org/10.1002/cmdc.202100644

Publisher: Wiley

Abstract: 
Tuberculosis represents one of the ten most common courses of death worldwide and the emergence of multidrug-resistant M. tuberculosis makes the discovery of novel anti-tuberculosis active structures an urgent priority. Here, we show that (+)-floyocidin B representing the first example of a novel dihydroisoquinoline class of fungus-derived natural products, displays promising antitubercular hit properties. (+)-Floyocidin B was identified by activity-guided extract screening and its structure was unambiguously determined by total synthesis. The absolute configuration was deduced from a key synthesis intermediate by single crystal X-ray diffraction analysis. A hit series was generated by the isolation of further natural congeners and the synthesis of analogs of (+)-floyocidin B. Extensive biological and physicochemical profiling of this series revealed first structure-activity relationships and set the basis for further optimization and development of this novel antitubercular scaffold.

Harvard Citation style: Kleiner, Y., Pöverlein, C., Klädtke, J., Kurz, M., König, H., Becker, J., et al. (2022) The Discovery and Structure-Activity Evaluation of (+)-Floyocidin B and Synthetic Analogs, ChemMedChem, 17(6), p. e202100644. https://doi.org/10.1002/cmdc.202100644

APA Citation style: Kleiner, Y., Pöverlein, C., Klädtke, J., Kurz, M., König, H., Becker, J., Mihajlovic, S., Zubeil, F., Marner, M., Vilcinskas, A., Schäberle, T., Hammann, P., Schuler, S., & Bauer, A. (2022). The Discovery and Structure-Activity Evaluation of (+)-Floyocidin B and Synthetic Analogs. ChemMedChem. 17(6), e202100644. https://doi.org/10.1002/cmdc.202100644