A NHK approach towards the total synthesis of the cornexistins

Aimon, Anthony (2013) A NHK approach towards the total synthesis of the cornexistins. PhD thesis, University of Glasgow.

Full text available as:
[img]
Preview
PDF
Download (10MB) | Preview

Abstract

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.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Cornexistin, Hydroxycornexistin, NHK, herbicide, herbicidal activity, Nozaki, Hiyama, Kishi, nine-membered ring, medium sized ring, total synthesis
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Funder's Name: UNSPECIFIED
Supervisor's Name: Clark, Prof. James Stephen
Date of Award: 2013
Depositing User: Dr Anthony Aimon
Unique ID: glathesis:2013-4572
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Sep 2013 08:08
Last Modified: 13 Sep 2013 08:10
URI: http://theses.gla.ac.uk/id/eprint/4572

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year