Research Opportunity Number: CHE-06
Project Title: Toward Convergent Syntheses of the Taccalonolides and Related Compounds
Project Summary: The taccalonolides are structurally intricate natural products with great potential as therapeutics for the treatment of human cancers. They act by inhibiting cellular mitosis by binding to microtubules and display potent activities against cancer cells that are resistant to our existing armamentarium of cancer drugs.
The taccalonolides are challenging, perhaps even formidable, objectives for chemical synthesis. However, there is the possibility that chemical concepts and reactions could be developed to produce these drug candidates by controlled mergers of prefabricated molecular fragments.
This project is leveraging a set of powerful structure-building reactions in an effort to construct these compounds in the laboratory. This project could uncover a family of structurally simplified taccalonolides that are accessible by the methods of organic synthesis and retain the potent microtubule-stabilizing properties of the naturally occurring agents.
This project will place a premium on the development of reaction sequences that display high levels of efficiencies and margins of stereochemical control.
Student Roles and Responsibilities: The Student will shadow the Mentor and conduct chemical reactions under the supervision of the Mentor (at all times). Laboratory safety is crucial. The Student will gain knowledge about how chemical reactions are performed safely. They will also learn how sequences of chemical reactions are used to accomplish laboratory syntheses of structurally intricate compounds with potentially important therapeutic properties.
Various reagents, solvents, and chemical building blocks will be utilized by the Mentor and Student in this project. Reactions will be conducted in dry glassware (i.e. flasks) and under an inert atmosphere of nitrogen or argon in a well-ventilated hood for chemical research. Magnetic stir plates, rotovaps, and various types of glassware (e.g. separatory funnels and glass chromatography columns) will also be used in this project. Hazardous reagents such as lithium aluminum hydride, trimethyl aluminum, and tert-butyl lithium will not be utilized by the Student. Chemical safety data sheets will be reviewed carefully before the Student is allowed to utilize a particular chemical in this project. The Student will be required to undergo our department's laboratory safety training before they are permitted to participate on this project.
Additional Considerations: Organic synthesis is a unique form of “hand off construction” wherein two or more molecules (i.e. reaction partners) are combined under controlled conditions and undergo a chemical change that was designed by the chemist.
The student on this project will gain a working knowledge of diverse reactions that are well known to the field of organic synthesis. These reactions include the formation and use of enolate ions to produce new carbon-carbon bonds, the use of carbon-based nucleophiles in carbonyl addition reactions, and the execution of pericyclic reactions to produce substituted cyclic compounds.
These reactions will be performed in common laboratory solvents in a well-ventilated hood in the Mentor's laboratory. The student will wear safety glasses, a lab coat, and gloves at all times in the laboratory and will be taught how to perform chemical reactions safely. The student will also learn how to execute and quench chemical reactions and become proficient at purifying reaction products by chromatographic methods (e.g. silica gel chromatography).
The student will also be taught how chemists utilize spectroscopic methods (e.g. NMR spectroscopy) to elucidate the structures of the compounds they produce in these reactions.
Department/Institute: Department of Chemistry
Participation Dates: June 23 – August 15, 2025
Stipend Offered: $0
Number of Internships Available: To Be Determined
Application Deadline: March 15, 2025, midnight Eastern Daylight Time