Towards the synthesis of the cornexistins

Doctoral Dissertation

Abstract

Cornexistin 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.

Attributes

Attribute NameValues
URN
  • etd-07202007-012537

Author James Chenkuo Tung
Advisor Richard Taylor
Contributor Richard Taylor, Committee Member
Contributor Marvin J. Miller, Committee Member
Contributor Olaf Wiest, Committee Member
Contributor Xavier Creary, Committee Member
Degree Level Doctoral Dissertation
Degree Discipline Chemistry and Biochemistry
Degree Name Doctor of Philosophy
Defense Date
  • 2007-07-13

Submission Date 2007-07-20
Country
  • United States of America

Subject
  • nine membered ring

  • cornexistin

  • ring closing

Publisher
  • University of Notre Dame

Language
  • English

Access Rights Open Access
Content License
  • All rights reserved

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