MYRIAPORONES: SYNTHETIC AND BIOLOGICAL STUDIES

University Of Notre Dame, Notre Dame IN

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Abstract

Small molecule natural products represent a valuable collection of ligands for use in the study of protein and cellular function. A detailed understanding of receptor-ligand interactions at the molecular level will allow for the design and preparation of new chemotherapeutic agents. Specifically, the relationship between conformation and biological activity of a novel class of complex natural products is being investigated. The power of synthesis in combination with high field nuclear magnetic resonance (NMR) and computer-based molecular modeling analysis is being used to investigate the biological activity of a novel class of natural product at the molecular level. A new class of natural product, myriaporones, has been identified as an exciting lead in the search for the next generation of cancer chemotherapy. Their structural similarity to the potent macrolide tedanolide leads one to consider a related biological mode of action. Practical synthetic routes to myriaporone 1 and myriaporone 4 are presented. The development of new synthetic methodology for the stereoselective creation of hydroxypropionate structural units, allylic alcohols, and poly-trisubstituted olefins is also proposed. Receptor isolation studies as well as biological activity data and conformational analysis of the parent compounds and analogues will provide new information about the details about the molecular mode of action of these interesting compounds.