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Biomimetic Cascade Reactions Towards the Synthesis of Ciguatoxin

Title: Biomimetic Cascade Reactions Towards the Synthesis of Ciguatoxin.
Name(s): Bou Hamdan, Farhan Ramez, 1979-, author
Holton, Robert A., professor directing dissertation
Keller, Laura L., outside committee member
Schwartz, Martin A., committee member
Krafft, Marie E., committee member
Logan, Timothy M., committee member
Department of Chemistry and Biochemistry, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2007
Publisher: Florida State University
Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Considerable attention has recently been given to the preparation of the ciguatoxins, the major group of toxins implicated with the onset of ciguatera fish poisoning (CFP) – a seafood-borne illness associated with the consumption of reef fish in tropical and subtropical areas. Ciguatoxins are characterized by a very complex polycyclic framework of 13 ether rings ranging from five to nine members. Previous studies directed towards the synthesis of the ciguatoxin skeleton have illustrated the difficulty associated with the construction of medium rings, particularly eight and nine-membered. We envisaged that an electrophile-induced epoxy-alcohol cascade cyclization, previously developed in our laboratory and utilized in the synthesis of hemibrevetoxin-B, could be used for the construction of medium-ring ethers. As little was known about this cyclization cascade, an investigation has been launched to test the potential of this biomimetic approach in the construction of [6,8]-trans-fused bicyclic ethers and its applicability towards the synthesis of the HIJ rings of the ciguatoxins. This study has revealed that the construction of oxocanes via this epoxy-alcohol cascade cyclization methodology is feasible, and that molecular tethers facilitate the reaction. Several tethers including a benzene ring, a cis or trans-fused dioxolane were tested. Interestingly, the use of a dioxolane tether has demonstrated that a considerable level of diastereocontrol can be obtained. Moreover, the incorporation of the nucleophilic alcohol group within a cyclic structure has proven to have a large effect on the Baldwin vs. anti-Baldwin selectivity. A theoretical study regarding that aspect has further supported our findings. Finally, this work has resulted in the synthesis of an advanced tricylic intermediate of the ciguatoxin skeleton. It is one of the most efficient pathways reported so far, as it provides this advanced intermediate in 23 linear steps and 11% overall yield.
Identifier: FSU_migr_etd-3506 (IID)
Submitted Note: A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Degree Awarded: Spring Semester, 2007.
Date of Defense: November 9, 2006.
Keywords: Oxocanes, Cascade Cyclizations, Electrophile induced Cyclizations, Trans-Fused Polyethers, Ciguatoxin
Bibliography Note: Includes bibliographical references.
Advisory Committee: Robert A. Holton, Professor Directing Dissertation; Laura L. Keller, Outside Committee Member; Martin A. Schwartz, Committee Member; Marie E. Krafft, Committee Member; Timothy M. Logan, Committee Member.
Subject(s): Biochemistry
Molecular biology
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Host Institution: FSU

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Bou Hamdan, F. R. (2007). Biomimetic Cascade Reactions Towards the Synthesis of Ciguatoxin. Retrieved from