Date Thesis Awarded

5-2021

Access Type

Honors Thesis -- Access Restricted On-Campus Only

Degree Name

Bachelors of Science (BS)

Department

Chemistry

Advisor

Dana Lashley

Committee Members

Robert J. Hinkle

Rachel O'Brien

Oliver Kerscher

Abstract

Natural products are organic molecules produced by living organisms in nature. Many of them exhibit interesting biological activities and have pharmaceutical potential. However, they exist in only very small amounts in nature which poses a limitation in the discovery of their medicinal properties; therefore, synthesizing natural products in the lab in sufficient amounts is meaningful to enable scientists to better study their properties. Quinones are a class of very versatile organic molecules, ubiquitously in living organisms. Many quinones are involved in biological functions, such as the electron transport chain. This paper is divided into two projects involving quinone natural product synthesis. The first project describes the synthesis of 3- methylbuteneoxide-1,4-anthraquinone (3.8), which is a mitochondrial complex I (MCI) inhibitor with an IC50 of 5 μM, utilizing substrate-based inhibitor design. Compound 3.8 also has high inhibitory selectivity for MCI when tested against other quinone-converting enzymes, including succinate dehydrogenase, and the Na (+)-translocating NADH:quinone oxidoreductase. Additionally, it also shows anti-cancer proliferation properties comparable to doxorubicin in cell-based proliferation assays. The second project describes the discovery of a cyclization reaction yielding the natural product and potent anti-cancer agent Chimaphilin, which was discovered during the optimization of the reaction in the first project. Reaction optimization, the proposed mechanism, and regioisomer identification are discussed.

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