Natural products as a rich source of pharmaceuticals and innovative chemical transformations: platform development for the generation of new antiviral drugs, antifeedant terpenoids, and novel methodology for chemical synthesis
Final Report Abstract
Natural products have inspired us throughout this project: We developed the first and only modular synthesis of antibiotic meroterpenoids, realized a highly convergent route to more than 15 antifeedant leucosceptroids and established the first one-pot b-halogenation of enones. It was exciting to see that several tetracyclic meroterpenoids possess highbiological activity against MRSA strains. These results are a good starting point for future structure-activity relationship (SAR) studies with the ultimate goal to develop new antibiotics against gram-negative bacteria (the Holy Grail in antibiotic research). With this project, we also want to spark further interest in the community to focus on antibiotic research. The importance of the obtained results was also recognized by the Austrian Press Agency (APA) and several newspapers. The fact that we could shine light on the biosynthesis of the leucosceptroids inspired us to investigate the related and equally fascinating natural product dictyoxetane. In the case of the latter we investigated a bioinspired synthesis that ultimately led to a revised biosynthesis. In addition, our studies revealed that dictyoxetane is unable to inhibit bacteria and cancer cells.
Publications
- A Modular Synthesis of Tetracyclic Meroterpenoid Antibiotics. Nat. Commun., 2017, 8, 2083
R. Wildermuth, K. Speck, F.- L. Haut, P. Mayer, B. Karge, M. Brönstrup, T. Magauer
(See online at https://doi.org/10.1038/s41467-017-02061-7) - Bioinspired Total Syntheses of Terpenoids. Org. Biomol. Chem. 2017, 15, 12–16
C. L. Hugelshofer, T. Magauer
(See online at https://doi.org/10.1039/c6ob02488b) - De Novo Synthesis of Benzannelated Heterocycles.Chem. Eur. J., 2017
J. Feierfeil, T. Magauer
(See online at https://doi.org/10.1002/chem.201705662) - Development of a β-C–H Bromination Approach Towards the Synthesis of Jerantinine. J. Org. Chem., 2017, 82, 7410–7419
E. T. Huber, T. Unzner, C. Gerlinger, T. Magauer
(See online at https://doi.org/10.1021/acs.joc.7b01095) - Dyotropic Rearrangements in Natural Product Synthesis and Biosynthesis. Nat. Prod. Rep., 2017, 34, 228–234
C. L. Hugelshofer, T. Magauer
(See online at https://doi.org/10.1039/c7np00005g)
