Natural products (NPs) have been, and continue to be the corner stone of the drug discovery world. Either through natural products themselves or the synthetic methodology generated in the aims of accessing these all-important agents, they continue to drive multiple of fields of drug discovery. While the isolation of NPs continues, the discovery of new potent cytotoxic agents has been on the decline. With the introduction of robotics to the drug discovery process, NPs have been replaced with small molecule libraries bearing little similarities to NPs with regard to physicochemical properties; which are assumed to translate into complex three-dimensional activity in biological settings. The decline in the isolation of cytotoxic NPs, coupled with the over use of non-complex screening libraries has inadvertently led drug discovery down a path that has limited the discovery of new agents that modulate complex three-dimensional biological targets in the search for new potent therapeutic agents. While numerous groups have developed new strategies at the construction of chemical screening libraries, in which many have shown great potential and impact, they are still limited in their applications. Our laboratory in the efforts to contribute in the field of bioactive agent discovery and synthesis has developed a new strategy at the diversification of intermediates within total synthesis routes. To be presented are our currents efforts in the diversification of the intermediates within our total synthesis routes of the uvaretin, brocazine, and balgacyclamide family of natural products. Through the campaigns towards these NPs, our laboratory has discovery new positive potentiating agents (allowing a nearly 30% reduction of doxorubicin dosage while retaining cytotoxicity), the discovery of new transcription factor stabilizing small molecules, new bioactive agents, and the construction of a new class of chemical screening library that is tunable, transformative, and adaptable for multiple high-throughput based research campaigns.  <br/>

Exploiting synthesis inherent in total synthesis campaigns: New avenues for bioactive agent discovery

2019 Spring National Meeting

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