Total Synthesis of Gukulenin A

• Applicant: Professor Dr. Martin Hiersemann
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 344336255

In summary, we envision the completion of the first total synthesis of a marine bis(tropolonoid) tetraterpenoid from the natural product family of the gukulenins. The gukulenins are isolated from samples of the red marine sponge Phorbas Gukulensis. The gukulenins have been shown to be potent cytotoxics for various cancer cell lines in vivo and in vitro (gukulenin A). Seven of the eight gukulenins isolated to date exhibit a unique hexacyclic bis(α-tropolonoid) molecular architecture with ten centers of chirality and one axis of chirality. The structural elucidation of gukulenins has so far been based on the interpretation of NMR experiments and will be verified by our total synthesis of gukulenin A. Our motivation for the total synthesis of gukulenin A stems first from the unique molecular architecture of the natural product. Total synthesis of gukulenin A requires innovative synthesis method development due to the unprecedented target molecule architecture. With the further development of the de Mayo reaction, we have already made a visible contribution in this respect during the first funding period. Further synthesis method development is also essential in the second funding period, especially with regard to chemistry with and on α-tropolones. If our project is successful, we will be able to support further studies on the biological activity of gukulenins despite limited availability from the marine sponge.

• DFG Programme: Research Grants