FIRST TOTAL SYNTHESIS OF NAGELAMIDE W AND DEVELOPMENT OF NITROGEN CONTAINING HETEROCYCLIC COMPOUNDS AS 20S PROTEASOME MODULATORS
Nitrogen-containing heterocyclic compounds are vital in organic chemistry due to their unique properties and reactivity, playing key roles in pharmaceuticals, agrochemicals, and functional materials. Over 75% of FDA-approved drugs include these heterocycles, underscoring their importance in modern medicine. The discovery of novel N-heterocyclic compounds with significant biological activities is rapidly expanding, driven by advances in synthetic methodologies like transition metal-catalysis and biocatalysis.Looking ahead, the importance of N-heterocyclic compounds is expected to grow. The advent of new technologies and an increasing understanding of disease mechanisms will likely drive the demand for novel pharmaceuticals incorporating nitrogen heterocycles. This trend is anticipated to lead to the discovery of new drugs with improved efficacy and safety profiles, addressing unmet medical needs and enhancing patient outcomes. This dissertation focuses on developing new methods for synthesizing N-heterocyclic compounds, specifically pyrazoles and pyridines, through reactions of epoxides with hydrazine and ammonia, respectively. Both established and novel methodologies were also utilized to synthesize the nitrogen-containing natural product nagelamide W in 11 linear steps, resulting in an overall yield of 6%. Additionally, N-heterocyclic compounds were evaluated as 20S proteasome modulators and used as chemical probes to elucidate their binding sites on the 20S proteasome. These efforts aim to enhance the understanding and application of N-heterocycles in medicinal and biological sciences.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- Attribution 4.0 International
- Material Type
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Theses
- Authors
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George, Dare E.
- Thesis Advisors
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Tepe, Jetze J.
- Committee Members
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Huang, Xuefei
Karen, Karen
Maleczka, Robert
- Date Published
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2024
- Subjects
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Chemistry, Organic
- Program of Study
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Chemistry - Doctor of Philosophy
- Degree Level
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Doctoral
- Language
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English
- Pages
- 353 pages
- Permalink
- https://doi.org/doi:10.25335/qq02-q782