The research team was able to accomplish several breakthroughs for the project. We were able to accomplish and scale up the first total synthesis of salimabromide. This molecule has been isolated only once in minute quantitates (0.5 mg) and has eluded its synthesis as well as re-isolation since then. The devleoped synthetic sequence is robust enough to be conducted on multi-gram scale, enables deep-seated structural modifications and set the foundation for structure-activity-relationship studies. The optimized route enabled us to prepare 296 mg of salimabromide in a single batch. During these studies, we discovered a powerful method for the construction of vicinal all-carbon stereocenters from readily available neopentylic epoxides. The developed transformation benefits from mild reaction conditions proceeding in a temperature range from 0 to 23 °C. Systematic variation of the terminating (hetero)arene and selected modifications of the remote substitution pattern provided a wealth of structurally unique, previously unknown tetralin and chromane systems. Investigation of the migration tendencies of various substituents revealed an unusual disproportionation pathway for which we performed computational studies to support the putative reaction mechanism. In collaborative work with Prof. Werz (University of Jena) salimabromide was found to display a novel stimulating priming effect on lipid mediator formation, being cell type/stimulus specific and not cytotoxic. The ring-expansion of chlorinated/brominated cyclopropanes proceeds under mild conditions employing simple 1-indanones of which more than 60 substrates are readily available from commercial suppliers. The method is robust enough to allow for rapid access to structurally diverse analogs as demonstrated in the synthesis of the natural product defucogilvocarcin M. While investigating several methods to accomplish oxidation of a crucial defucogilvocarcin precursor, we also discovered a (transition)-metal free conditions to selectively oxidize the benzylic position of isochromanes. In addition, we discovered a unique dearomatization of halogenated naphthols that warrants further investigations. The investigated point-to-axial chirality transfer enabled synthesis of an enantiomerically enriched biaryl for the first time. Based on these studies, we realized a general synthetic entry to Ganoderma natural products. The developed strategy enabled access to the applanatumols, meroapplanin, lingzhilactone and lingzhiol. The successful application of a rare photo-Fries reaction and the incorporation of a recently disclosed photoredox catalyzed process highlights the potential of photochemistry for natural product synthesis. The realization of the decarboxylative oxidation process has also implications for the biosynthesis of these natural products. We were also able to synthesize the oxepin core of psammaplysin and provided an overview about synthetic methods to access this fascinating motif. In this context, we also obtained detailed insights in the behaviour of substituted oxepins. The envisioned C–F activation of work package 2 provided several key insights but turned out to be highly limited to a small subset of substrates. We therefore shifted our focus on the advancement of work package 1. The results of the project were described in eight high-impact publications, presented on more than 35 occasions to the scientific community - 10 selected presentations: University of Oxford, GDCh-Wissenschaftsforum, Basler Chemische Gesellschaft, Bayer Crop Science, University of Cologne, Firmenich, MIT, SCRIPPS BiCoastal Seminar, Caltech, UCSD). The result and impact of our research were also shared with the public, for instance via press releases, the Wissensdurst Festival and most recently via an OEAW Young Science talk. The research team has been very successful and all previous team members have received offers from academia and industry.
