Aglycon Modifications of Ipomoeassin F: Synthetic Route Development and Analog Synthesis to Enable Further SAR Studies

<p>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. </p>

Name thesis:degree_name

Doctor of Philosophy in Chemistry (PhD)

Level thesis:degree_level

Dissertation

Year dc:date.available

2019

Author dc:creator

• Barber, Eric

Advisor dc:contributor.advisor

• Shi, Wei

Contributors dc:contributor

• Zheng, Nan
• Stites, Wesley E.

• Ipomoeassin
• macrocycle
• metathesis
• Resin Glycoside
• Organic Chemistry

Repository record dc:identifier

https://scholarworks.uark.edu/etd/3537

OAI identifier oai:identifier

oai:scholarworks.uark.edu:etd-5087