Tuesday, November 26, 2024
11/26/2024
Project Summary/Abstract The detailed study of the fundamental chemistry and biological properties of complex natural products provides critical insight toward understanding their mode of action and enables development of new approaches for treatment of various human ailments. This research program focuses on the development of efficient and concise strategies for the total chemical syntheses of structurally complex and biologically active natural products. The target compounds are selected based on novelty of molecular architecture and associated challenges, paucity of prior synthetic studies, abundance of opportunities for development of new synthetic strategies and methodologies, possession of significant biological activity, and the potential for future chemical and biological studies. The systematic discovery, development, and application of new synthetic strategies and methodologies explored in this program continue to provide synthetic samples of rare and precious compounds for structure validation and detailed examination of their chemistry and biology. This program focuses on synthetic studies of the rich families of complex natural products including cyclotryptamine, diketopiperazine, and monoterpene indole alkaloids. A central interest is the development of generalizable directed, regioselective, stereoselective, and efficient union of complex fragments providing late-stage couplings to secure challenging linkages, including complete stereocontrol at quaternary stereogenic centers. Convergent and guided assembly of advanced fragments is complemented by development and application of new highly selective chemical transformations for the rapid generation of molecular complexity. These transformations include new methods for amide derivatization, azaheterocycle syntheses, cascade bond–forming reactions involving enamines, stereoretentive hydroxylation of complex substrates, and stereocontrolled sulfidation made possible through employing new reagents and conditions developed in this program. This program’s access to potently bioactive collection of families of complex alkaloids and related derivatives continues to enables exciting biochemical collaborative investigations. The array of synthetic molecules accessed through this program behold great promise as new bioactive compounds and mechanistic tools, and these compounds are continually evaluated and examined through multidisciplinary collaborations.
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