Atom economic rhodium-catalyzed synthesis of lactones as key step for the construction of natural macrolactones

• Applicant: Professor Dr. Bernhard Breit
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 315326950

Makrolactones as well as Makrodiolides represent important classes of natural products with a wide range of biological activities. The development of efficient catalytic methodology for their intrinsic waste-free i.e. atom economic synthesis under direct construction of the lactone function is basically unknown. Hence, the goal of this project is the development of a generally applicable atom economic and stereoselective macrolactonization applying an atom economic rhodium-catalyzed intramolecular addition of carboxylic acids to terminal alkynes and allenes. Subsequent to establishing this method its utility shall be probed in the context of the total synthesis of two biologically and medicinally interesesting natural product families, the epothilones B, D, and F as respresentatives for the class of macrolactones, and Samroiytmycin A as a representative for the class of macrodiolides. The envisioned synthesis strategy would enable a flexible late stage functionalization of the macrolactone and macrodiolide cores thus enabling a simple access to potentially biologically active compounds. The so-obtained natural product derivatives shall be tested with regard to their biological activities together with the Helmholtz-Institute for Pharmaceutical Research in Saarbrücken.

• DFG Programme: Research Grants