A Roundtrip from Methodology Development via Total Synthesis to Biology and Back

Total synthesis of relevant natural products is indispensable for the investigation of their formation, the understanding of their biological function and the design of analogs that may have a favorable therapeutic potential. To access such compounds as efficiently as possible, we develop tandem reactions based on oxidative electron transfer that is basically the bridge between different intermediate types and their reactivity patterns. This requires that fundamental questions concerning the mechanism and scope of such processes must be answered. Our oxidative domino processes allow the flexible use of multiple intermediate types in the individual sequence steps. This is inspired by Nature where complex natural products are often assembled by reaction cascades with an unprecedented efficiency. In this respect, we are especially interested in the chemistry and biochemistry of autoxidatively formed lipid metabolites, of alkaloids, lignans and terpenes. The biological properties of the synthesized natural products are evaluated, and synthetic analogs of them are derived what requires the development of new methodology again.