Total synthesis of jerangolides

• Applicant: Professor Dr. Johann Jauch
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280969177

Jerangolides are scundary metabolites from the myxobacterium Sorangium cellulosum. These natural products show antifungal activity. Recently, the group of Prof. Rolf Müller, Pharmazeutische Biotechnologie, Universität des Saarlandes, found that the jerangolides are highly potent inhibitors of the generation of multi-cell fruiting bodies of Myxococcus xanthus, another myxobacterium from the suborder Myxococcales. To study this pharmacological activity in detail, large amounts of the jerangolides as well as derivatives thereof with affinity tags are required. Therefore, we want to develop total syntheses of all known jerangolides. Based on a local symmetry in these natural products, these syntheses can be designed very short and efficient (only half the number of steps of already published syntheses of selected jerangolides). Notably, our synthetic plan allows the synthesis of all jerangolides with the same strategy. The synthesis of well-defined stereo isomers of the jerangolides B, E and H offers the possibility to determine the configuration of a stereocenter with unknown chirality. Furthermore, with our strategy we can easily synthesize numerous analogues to additionally elucidate structure-activity relationships.

• DFG Programme: Research Grants