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.

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
• 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: https://theses.gla.ac.uk/id/eprint/4572