Natural Products Chemistry: Total Synthesis, Synthetic Methodology, NMR-Studies and Biomolecular Evaluation
The exquisite and varied architectures of natural products provide a rich pallet for discovery, whether these are used to probe biological mechanisms or to provide the basis for pharmaceutical drug discovery, natural metabolites continue to command attention. For many of these reasons, we are drawn to these structures as testing grounds for synthetic strategies and the development of new methods.
Prominent examples, which have been targeted in our group, include a range of macrolides, such as archazolid, a potent V-ATPase inhibitor, rhizopodin, which interacts with actin, antifungal leupyrrin, the RNA polymerase inhibitor etnangien, as well as linear polyketides, such as the antifungal ajudazols or tuscorones, but also hindered polycyclic compounds, such as dysidavarone or salimabromide, but also natural product analogues such as 3-Lipid II. By application of extensive high field NMR studies, including J-based configuration analysis, molecular modeling and chemical methods, in combination with bioinformatics analyses based on gene-cluster data, the full stereo-structures of many of these metabolites was delineated in our group. Furthermore, convergent and in particular modular strategies for their syntheses have been developed, which have culminated in elaborate the total syntheses of these metabolites, and many of these compounds were prepared for the first time in our group. Along these lines, novel methodologies were established, including novel domino sequences based on sequential catalytic processes for the rapid assembly of key structural features of these complex natural products. In addition, biomolecular studies have been initiated for some of these compounds allowing for a more detailed understanding of target inhibitor interactions at a molecular level.