Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


NKenton_Dissertation_Final2.pdf (12.64 MB)

ETD Abstract Container

Abstract Header

Total Synthesis of Azaspiracid-3, C20-epi-Azaspiracid-3, and Structural Definition of the Azaspiracids

Kenton, Nathaniel T
http://rave.ohiolink.edu/etdc/view?acc_num=osu1523545452232749

Abstract Details

2018, Doctor of Philosophy, Ohio State University, Chemistry.
The azaspiracids are structurally complex marine toxins that have been linked to seafood-borne illness since their discovery in 1995 and structural elucidation in 1998. The azaspiracids, even at low concentrations, have an abnormally broad set of acute and chronic health effects, including damage to the thymus, intestine, lungs, pancreas, and liver; tumor promotion in mice; teratogenicity in fish; and severe gastrotoxic symptoms: nausea, diarrhea, and vomiting. The mechanism(s) of action, however, are largely unknown. In order to more fully understand the risks associated with azaspiracid exposure and to establish sensible regulatory limits, samples of the compound must be made available to biologists. Azaspiracids are largely unavailable from natural sources, as the extraction procedure is demanding and the concentration of the substance in seafood is typically very low; as such, the most efficient method to acquire significant quantities of the compound may be through chemical synthesis. In the work described here, the previously-accepted structure of azaspiracid-3 was synthesized for the first time and shown to be non-identical to the natural product. A series of experiments, culminating in a total synthesis of the true structure, identified the C20 stereochemistry of the natural product as being epimeric to the expected structure. Because 1H-NMR data for the C19 and C20 methine protons among all known azaspiracids are very similar, a general stereochemical correction at C20 for this family of molecules is necessary. 5.5 mg of purified, natural azaspiracid-3 was produced.
Craig Forsyth, PhD (Advisor)
Thaliyil Rajanbabu, PhD (Committee Member)
Jovica Badjic, PhD (Committee Member)
Jonathon Davis, PhD (Committee Member)
179 p.
Chemistry; Organic Chemistry
organic synthesis; natural products; marine toxins; azaspiracid

Recommended Citations

Citations

  • Kenton, N. T. (2018). Total Synthesis of Azaspiracid-3, C20-epi-Azaspiracid-3, and Structural Definition of the Azaspiracids [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1523545452232749

    APA Style (7th edition)

  • Kenton, Nathaniel. Total Synthesis of Azaspiracid-3, C20-epi-Azaspiracid-3, and Structural Definition of the Azaspiracids. 2018. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1523545452232749.

    MLA Style (8th edition)

  • Kenton, Nathaniel. "Total Synthesis of Azaspiracid-3, C20-epi-Azaspiracid-3, and Structural Definition of the Azaspiracids." Doctoral dissertation, Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1523545452232749

    Chicago Manual of Style (17th edition)

osu1523545452232749
313
© 2018, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.