Other projects

Natural products related to infectious diseases. We have extensively explored the chemistry of mycolactones, which form a family of complex macrolactones that are produced by different strains of Mycobacterium ulcerans. Mycolactones A/B are the causative agents for Buruli ulcer, a disfiguring skin disease with a high prevalence in sub-Saharan Africa. We have developed a new, RCM-based total synthesis of these complex macrolactones (Gersbach et al., 2011) to provide pure and well characterized material for biological studies (collaboration with Prof. G. Pluschke, Swiss Tropical and Public Health Institute, and Prof. D. Neri, ETHZ).

Apart from natural mycolactones A/B we have also prepared number of non-natural variants for structure/toxicity studies (manuscripts in preparation).

Over the last 12 months we have initiated synthetic work on natural products with reported activity against Mycobacterium tuberculosis. In both cases, the goals of the project are the establishment of a total synthesis, the synthesis of analogs for SAR studies, and, ultimately, the identification of potential drug candidates against tuberculosis (TB) (in a collaboration with Prof. Stewart Cole, EPFL, Lausanne, and other consortium members of the EU FP7 project “More Medicines for Tuberculosis”, MM4TB).

Gersbach, P., Jantsch, A., Feyen, F., Scherr, N., Dangy, J.-P., Pluschke, G., Altmann, K.-H. A RCM-Based Approach to Mycolactones A/B. Chemistry Eur. J., in press.

We have recently completed the total synthesis of the plant-derived natural product valerenic acid, employing the monoterpene R-pulegone as a chiral starting material (Kopp et al., 2009).

Valerenic acid is one of the major constituents of valerian and has been shown recently to act as a modulator on the GABA_A receptor. In collaboration with Profs. Hanns Moehler, University of Zürich, and Erwin Sigl, University of Bern, we explored part of the SAR of this bioactive natural product and we have found tetrazole 5 to be a ca. 20-fold more potent GABA_A receptor modulator than the natural product valerenic acid (Kopp et al., 2010).

Kopp, S., Baur, R., Sigel, E., Moehler, H., Altmann, K.-H., Highly Potent Modulation of GABAA Receptors by Valerenic Acid Derivatives. ChemMedChem, 2010, 5, 678-681.

Kopp, S., Schweizer, W. B., Altmann, K.-H., Total synthesis of valerenic acid. Synlett, 2009, 1769-1772.