Identifier

etd-04112011-173742

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

The first part of the work is dedicated to the selective detection of Homocysteine (Hcy). In order to better understand this colorimetric detection method, a thermodynamic model for the pH dependence of the effective reduction potential of Hcy derived á-carbon radicals has been proposed. And using viologen indicators of varying reduction potentials, we demonstrate that colorimetric changes occur at experimental pH values consistent with the model. The one-carbon bridge stereochemistry of bicyclo[3.3.1]nonane framework is critical to make the third ring of the tricyclic precursor of vinigrol. We studied this stereochemistry carefully and found that the major diastereomer formed from Robinson annulations places the one-carbon bridge substituent anti to the â-keto ester/amide unit introduced in the reaction and stereoselectivity appears to be kinetically controlled. The origin of this diastereoselection has been identified by density functional theory calculations. Efforts toward the total synthesis of vinigrol have been described. The tricyclic precursor of vinigrol has been efficiently synthesized in gram scale utilizing the Robinson annulation, base catalyzed epimerization and intramolecular alkylation as the pivotal steps. The thermal [2+2] reaction with dichloroketene remains in vain although several different approaches have been explored. Finally, an alternative route using the tricyclic enone as the electrocyclic reaction precursor has been investigated. This enone can be obtained from the tricyclic precursor via either a selenation- or a bromination-elimination sequence. Further transformation involving olefination, electrocyclic reaction and oxidative cleavage to generate the bridging eightmembered ring, would complete the synthesis of the vinigrol core.

Date

2011

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Crowe, William E.

Included in

Chemistry Commons

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