Natural products (NPs) and their structural scaffolds are a rich source of small molecule tools for chemical biology and drug candidates. In a novel approach, this proposal will investigate the combination of natural product fragments to form pseudo-natural products (pseudo-NPs) with uncharted biological activity. The purpose of this project is to explore the diastereo- and enantioselective synthesis of two pyrroquinoline scaffolds, a combination of pyrrolidine and tetrahydroquinoline fragments, and submit the obtained compound collections (>100 compounds) to phenotypical screening assays to assess their biological activity. The obtained molecules could potentially serve as novel biological probes and lay the foundation for the discovery of novel targets or drugs. Highly active compounds will be used to establish structure activity relationships (SAR) and design affinity isolation probes for the identification of cellular targets.
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