Exploiting iterative and bidirectional strategies for the rapid synthesis of the A-F fragment of ciguatoxin CTX3C

Alexander, Samuel David (2019) Exploiting iterative and bidirectional strategies for the rapid synthesis of the A-F fragment of ciguatoxin CTX3C. PhD thesis, University of Glasgow.

Due to Embargo and/or Third Party Copyright restrictions, this thesis is not available in this service.

Abstract

Ciguatoxin CTX3C and its congeners are marine polycyclic ethers with potent biological activities. Ciguatoxins all possess a trans/syn/trans fused polycyclic ether structure. They are produced mainly by the dinoflagellate, Gambierdiscus toxicus, and can be transferred up the food chain, to a variety of tropical and subtropical fish, most notably the moray eel. Ciguatoxins are the principal cause of ciguatera seafood poisoning, a debilitating illness that has been reported to last for decades in some cases.

The first chapter of this thesis provides an introduction to marine polycyclic ethers, exploring their origins, biosynthesis, toxicology and therapy. Prior syntheses of members of the ciguatoxin family by Sasaki, Hirama, Isobe, Kadota and Fujiwara are reviewed, with focus on the synthesis of the western fragment employed by each group. The methodology and bidirectional strategies developed by the Clark group are also reviewed.

The second chapter of the thesis concerns the construction of the A-F fragment of CTX3C. The general synthesis strategy exploits the pseudosymmetry which the ciguatoxins possess. This pseudosymmetric approach allows rapid access to the A-F fragment through a bidirectional RCM reaction and also iterative use of the Tsuji-Trost allylation reaction to provide an elegant approach to building C-C bonds.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: ciguatoxin, Tsuji-Trost, RCM, allylation, metathesis.
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Funder's Name: Engineering and Physical Sciences Research Council (EPSRC), Engineering and Physical Sciences Research Council (EPSRC), Engineering and Physical Sciences Research Council (EPSRC)
Supervisor's Name: Clark, Prof. J.S.
Date of Award: 2019
Embargo Date: 1 February 2022
Depositing User: Dr S. D. Alexander
Unique ID: glathesis:2019-40992
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 01 Feb 2019 16:50
Last Modified: 25 Mar 2019 13:36
URI: http://theses.gla.ac.uk/id/eprint/40992

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