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Title: A NHK approach towards the total synthesis of the cornexistins
Author: Aimon, Anthony
ISNI:       0000 0004 2740 2616
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2013
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Cornexistin and hydroxycornexistin were both isolated from the fungus Paecilomyces variotii. They were found to possess significant herbicidal activity, which triggered the interest of agrochemicals companies. Their structures consist of a nine-membered carbocyclic ring fused to a cyclic anhydride with various oxygen functionalities decorating the nine-membered core. Previously, the synthesis of (±)-5-epi-hydroxycornexistin was successfully achieved in the group, using a Stille-coupling reaction between a chloride and stannane fragments, followed by a key ring-closing metathesis reaction to form the core of the ninemembered ring. However, the desired stereochemistry on the C-5 centre could not be installed despite the use of a variety of methods. A new strategy, involving an intramolecular Nozaki-Hiyama-Kishi reaction was investigated, leading to the formation of an advanced intermediate for the synthesis of hydroxycornexistin. The reaction proved efficient and X-ray crystallography was used to confirm the desired formation of the natural C-5 configuration of cornexistins. The stereoselectivity of the reaction was considered and alternative methods to improve the diastereoisomeric ratio were attempted. The asymmetric synthesis of hydroxycornexistin was studied, using an advanced model substrate and an efficient strategy for the asymmetric syntheses of both Stille-coupling partners was performed. The synthesis of the chloride fragment involved a crossmetathesis reaction and a [3,3]-sigmatropic rearrangement reaction as main steps of the reaction sequence. Using a chiral auxiliary, the stannane fragment was obtained with excellent enantiomeric excess. Finally, the sequence leading to the synthesis of the NHK precursor was accomplished.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry