Date of Graduation

12-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Wei Shi

Committee Member

Nan Zheng

Second Committee Member

Wesley Stites

Third Committee Member

Matt McIntosh

Fourth Committee Member

Colin Heyes

Keywords

Ipomoeassin, macrocycle, metathesis, Resin Glycoside

Abstract

The ipomoeassin family of resin glycosides were discovered to have a high potency against numerous cancer cell line, with ipomoeassin F being the most potent among the family of natural products. Interestingly, one of the few differences between ipomoeassin F and the other compounds is the length of the fatty-acid derived aglycon. As the mechanism of action for this family of resin glycosides is unknown and didn’t have any significant COMPARE correlation with the recorded anticancer agents in the National Cancer Institute (NCI), further SAR studies are needed. Drawing on the differences between ipomoeassin F and the other ipomoeassins, it seemed logical to explore the effect of the aglycon on the bioactivity of these compounds. To achieve this, we sought to synthesize an epimer of ipomoeassin F, changing the configuration of the sole chiral center contained in the aglycon, as well as developing a synthesis that would enable us to modify the tail of the aglycon and explore in more depth the role of the critical region of the molecule.

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