Total and semi synthesis of natural product derived drugs

Natural products are a rich source of bioactive compounds with promising potential to be further developed into drug candidates. However, natural products often need to be chemically modified in order to improve their pharmacokinetic properties or increase their bio activity to serve as candidates for drug developement. 

Furthermore, some natural products have to be generated by total synthesis to be able to modify certain molecular positions or provide the compound in sufficient amounts.

One natural compound currently in focus of our research is Griselimycin, a cyclodepsi decapeptide which have been isolated from Streptomyces griselius, showing selective antimycobacterial activity including activity against MDR Mycobacterium tuberculosis. We are working on semi synthetic derivatization and total synthesis of novel Griselimycin derivatives in order to eliminate off-target effects and increase activity.

We also work on the total synthesis and semi-synthetic derivatization of different [13]cytochalasan-type natural products exhibiting strong actin binding and anti-biofilm activities. 

Selected publications:

NQO1-responsive Prodrug for in Cellulo Release of Cytochalasin B as Cancer Cell-targeted Migrastatic, M. D. Kagho, K. Schmidt, C. Lambert, L. Jia, K. Rottner, M. Stadler, T. Stradal,* P. Klahn*, ChemRxiv 2024, DOI: 10.26434/chemrxiv-2024-srxfv.

Discovery of Aminoratjadone Derivatives as Potent Noncovalent CRM1 Inhibitors, L. Jian, R. Zscherp, U. Beutling, X. Shen, S. Xu, X. Zhang, M. Brönstrup,* P. Klahn,* Q. Sun,*  J. Med. Chem. 2023, 66, 11940–11950; SSRN 2023, DOI: 10.2139/ssrn.4341553. (Communication)

Total Synthesis, Assingment of the Relative Configuration and Biological Evaluation of the Nitraria Alkaloid Nitrabirine, M. D. Kagho*, H. Hintersatz, A. Ihle, W. Colisi, H. Zeng, H. Schrey, P. Klahn*, M. Stadler, T. Rüffer, C. Bruhns, H. Lang, K. Banert, J. Org. Chem. 2021, DOI: 10.1021/acs.joc.1c01650; ChemRxiv  2021, DOI: 10.33774/chemrxiv-2021-f3r8h. (Communication)

Cannabinoids - Promising antimicrobial drugs or intoxicants with benefits?  P. Klahn, Antibiotics 2020, 9, 297.

New structural templates for clinically validated and novel targets in antimicrobial drug research and development, P. Klahn, M. Brönstrup, Curr. Top. Microbiol. Immunol. 2016, 365-417. How to Overcome the Antibiotic Crisis: Facts, Challenges, Technologies and Future Perspectives, Eds. M. Stadler, P. Dersch, Springer Verlag, 2016.)