The syntheses of kulkenon and sulfangolide

• Applicant: Professor Dr. Markus Kalesse
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 233345793

Sulfangolide and kulkenon are new secondary metabolites from myxobacteria. The sulfangolides are special since they were the first secondary metabolites from myxobacteria that exhibit a sulfate ester. Its structure was analyzed with the aid of NMR experiments and computer aided calculations. This structure elucidation set the background for our synthesis of both compounds. During the synthesis of kulkenon we realized that this structure elucidation was not describing the correct configuration at two stereocentres. Due to our work on kulkenon we could not only complete the first total synthesis of this natural product but also determine its correct configuration. We expect that this refinement will also apply to the sulfangolides. The synthesis of sulfangolide is to provide synthetic access to this unusual natural product and to provide an example of our vinylogous Mukaiyama aldol reaction and to show how this might shorten the number of steps during the synthesis of a complex natural product. Before, these fragments were constructed by either standard aldol and olefination protocols or by a classical vinylogous aldol reaction followed by a Mitsunobu inversion. Another unusual transformation is the intramolecular Heck reaction as macrocyclization protocol. Due to the fact that we had to re-investigate the configuration of kulkenon and restart its synthesis we used more time for this part of the project than initially planned. In addition, we encountered significant problems when performing the aldol connection between C16 and C17. The project is designed to complete the synthesis of sulfangolide and to confirm its configuration. As an additional methodological aspect we plan to investigate the aforementioned aldol reaction in detail since there are only few examples and some of these results seem to be contradictory.

• DFG Programme: Research Grants