Date of Graduation

8-2018

Document Type

Thesis

Degree Name

Master of Science in Chemistry (MS)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Shi, Wei

Committee Member

McIntosh, Matthias C.

Second Committee Member

Zheng, Nan

Keywords

Cytotoxicity; Fucose-truncated; Galactose; Ipomoeassin F; Macrolide; Monosaccharide

Abstract

Natural product synthesis has many applications in the field of chemical biology, due to the protein binding affinity to the complex three-dimensional structure. However, synthetic and structure-activity relationship studies concerning certain drug targets are scarce. For example, members of the ipomoeassin family have exhibited anti-cancer properties, but cost-effective optimization of these compounds has not yet been extensively studied. Ipomoeassin F, a natural glycoresin isolated from the leaves of the Ipomoea squamosa plant in the Suriname rainforest, has shown high cytotoxicity, with IC50 values measured at the low nanomolar range. Two studies by Postema and Fuerstner have outlined synthesis pathways for ipomoeassin F using ring closing metathesis (RCM) for macrolactonization. The Shi group improved the synthetic method by introducing the cinnamate and tiglate moieties at different stages and developing novel protecting group strategies to reduce the number of steps. Recently, extensive studies were conducted outlining structure-activity relationship; specifically of the fucose ring, cinnamate and tiglate functional groups, and lipophilic aglycone. Removal of the functional groups on the expensive fucoside moiety did not significantly affect the activity of the compound; therefore monosaccharide and galactoside analogues were designed, synthesized and biologically tested. The overall objective of this research is to explore the monosaccharide and galactoside analogue synthetic pathways in order to better understand the binding affinity and cytotoxic properties of ipomoeassin F.

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