Synthetic Studies towards Trichothecene Mycotoxins

Egan, Mark James (1991) Synthetic Studies towards Trichothecene Mycotoxins. PhD thesis, University of Glasgow.

Abstract

This thesis describes the first synthesis of a tetrahydroxylated trichothecene mycotoxin, 3alpha,4beta,8alpha,15-tetra-hydroxy-12,13-epoxy trichothec-9-ene (T-2 tetraol) (19), as its tetraacetate (Neosolaniol diacetate) (319) (Scheme 86). The synthetic strategy consists of five key elements. 1) formation of the cis fused AB ring system by a Diels-Alder cycloaddition; 2) formation of ring C by an intramolecular aldol reaction; 3) creation of the 3alpha,4beta-diol system of ring C by a stereoselective a-oxygenation/reduction protocol; 4) ring A enone formation via a regiospecific thermodynamically controlled alpha-selenylation, and 5) regio and stereospecific reduction of this enone to the required alpha-alcohol. As part of a concerted effort towards this molecule, this thesis reports a model study aimed at achieving the 3alpha,4beta-diol system of ring C (Scheme 52). The partial synthesis of 8-keto-anguidine (297) described herein (Chapter 2.2) allowed a study (Chapter 2.3) of the stereochemical outcome of the reduction of ring A enones by various reducing agents: it is shown that L-Selectride reduces such enones stereospecifically to 8alpha-alcohols. Attempted completion of an approach to deoxynivalenol (6) (Chapter 2.5) is discussed. The termination of this route is attributed to competing intramolecular processes which prevented successful olefination of the ketone (362).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1991
• Depositing User: Enlighten Team
• Unique ID: glathesis:1991-78272
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 28 Feb 2020 12:09
• Last Modified: 28 Feb 2020 12:09
• URI: https://theses.gla.ac.uk/id/eprint/78272