Type of Document Dissertation Author Tung, James Chenkuo URN etd-07202007-012537 Title Towards the synthesis of the cornexistins Degree Doctor of Philosophy Department Chemistry and Biochemistry Advisory Committee
Advisor Name Title Marvin J. Miller Committee Member Olaf Wiest Committee Member Richard Taylor Committee Member Xavier Creary Committee Member Keywords
- nine membered ring
- ring closing
Date of Defense 2007-07-13 Availability unrestricted AbstractCornexistin and hydroxycornexistin are natural products derived from the fungus
Paecilomyces variotti. Both cornexistin and hydroxycornexistin are highly potent
herbicides that have the unique quality of being harmless to corn plants. Because of this
quality, both molecules have attracted research interest from agrochemical companies.
Their interesting nine-membered ring structure contains a maleic anhydride and a key
exocyclic ethylidene; this structure also indicates membership in the nonadride family.
We targeted this interesting structure for total synthesis for both its fascinating biological
activity and its highly functionalized structure.
Cornexistin was found to be susceptible to retro-aldol opening and reclosure of its
nine-membered ring by workers at Dow Agrosciences. We targeted a retro-aldol
precursor through a series of aldol reactions. Utilizing a Johnson-Claisen rearrangement
and an enantioselective Evans-type aldol to generate the starting fragments, a series of
reactions was performed to find the appropriate conditions for a key bond-forming ester
enolate aldol. Oxidation of the product yielded a beta-ketoester that contained the complete
carbon skeleton of cornexistin.
Previous progress towards cornexistin included the use of a Diels-Alder reaction
to generate a [6.5] bicyclic system that was oxidatively cleaved to deliver a cyclononene
diketone. During the course of analyzing the relative stereochemistry of the Diels-Alder
reaction, analog synthesis and X-ray crystallography was used to unambiguously
determine the structure of the cycloadduct. Through ozonolysis, regioselective titanium-mediated olefination and further functional group manipulation, highly complex nine-membered
ring structures were generated. Finally, ring-closing metathesis and Tamao- Fleming oxidation produced the key ethylidene moiety of both cornexistin and hydroxycornexistin.
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