Details of Grant 

EPSRC Reference:	EP/R035423/1
Title:	Convergent Bidirectional Total Synthesis of Ciguatoxin CTX3C
Principal Investigator:	Clark, Professor J
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	School of Chemistry
Organisation:	University of Glasgow
Scheme:	Standard Research
Starts:	01 August 2018	Ends:	31 May 2022	Value (£):	724,061
EPSRC Research Topic Classifications:	Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:	Panel Date Panel Name Outcome 07 Mar 2018 EPSRC Physical Sciences - March 2018 Announced
Summary on Grant Application Form
The ciguatoxins and the other fused polycyclic ether natural products are produced by microscopic marine dinoflagellates and are found in a variety of organisms that feed on them as well as animals further up the food chain. The marine polyethers have exquisite molecular structures and are some of the largest and most complex compounds to have been isolated from natural sources. These natural products are amongst the most challenging targets currently confronting synthetic chemists because of the large number of interlocking rings and stereogenic centres they possess. For example, the marine polyether maitotoxin is the largest non-biopolymeric natural product known and only one of the 1.6 x 1029 possible stereoisomers of this compound corresponds to the natural product. Marine polyether natural products such as CTX3C possess potent and unique biological activities. For example, members of the brevetoxin and ciguatoxin families of marine polyether are potent neurotoxins. The ciguatoxins in particular are responsible for thousands of cases of human food poisoning every year and there have been many fatalities following the consumption of contaminated fish and seafood. As a consequence of their potent neurotoxic properties, analogues of the ciguatoxins have potential to function as probe molecules for the exploration of nerve signalling processes in vertebrates. Closely related marine polyethers also have potential as lead compounds for the development of new drugs. For example, the polyether natural product brevenal has been identified as an important candidate for the development of new treatments for cystic fibrosis and the gambieric acids possess potent anti-fungal activity that exceeds the activity of some agents used in the clinic. The goal of the research described in this proposal is the completion of a highly efficient and fully convergent total synthesis of the marine polyether ciguatoxin CTX3C. Construction of the target will be accomplished using a novel synthetic strategy that involves the deployment of novel iterative and bidirectional methods of ring construction for the rapid assembly of two polycyclic fragments that will coupled at a very late stage in the synthesis. It is expected that the synthesis of CTX3C will represent a step-change in terms of the synthesis of targets of high molecular complexity and will showcase novel and innovative tactics, strategies and methodology that will have relevance to other complex polycyclic natural products of structural and biological significance.
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