Chemistry and Interconversion of Complex Trichothecenes

Cameron, Stuart (1987) Chemistry and Interconversion of Complex Trichothecenes. PhD thesis, University of Glasgow.

Abstract

The trichothecenes are a ubiquitous group of toxic fungal sesquiterpenoids. Previous studies have shown that the 12,13-epoxide present in the trichothecenes may be crucial for biological activity. To gain further insight into the biological role of the epoxide, successful employment of the Sharpless deoxygenation protocol has been achieved after extensive model studies. This procedure gave the 12,13-exomethylene compounds (119) and (121) from the corresponding epoxytrichothecenes, namely triacetoxyscirpene (63) and triacetyldeoxynivalenol (120). In an extension to this work, Sharpless deoxygenation furnished the key intermediate, olefin (124), which was used to synthesise the 12,13-epi-epoxytrichothecene (128) via ozonolysis and reaction of the derived norketone (125) with dimethylsulphonium methylide. Both the Sharpless deoxygenation product (119) and the epi-epoxytrichothecene (128) were found to be essentially non-toxic, thus demonstrating for the first time the necessary presence of the epoxide and its stereochemical definition. Further work has led to methodology for the provision of less readily available trichothecenes. To this end, deoxynivalenol (23) has been successfully synthesised from one of our culture products, anguidine (9), via another naturally occurring trichothecene, calonectrin (5). This methodology involved selective removal of the C-4 oxygen functionality, selective allylic oxidation at C-8, to establish the enone system, and introduction of the C-7 hydroxyl moiety.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1987
• Depositing User: Enlighten Team
• Unique ID: glathesis:1987-77572
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 09:05
• Last Modified: 14 Jan 2020 09:05
• URI: https://theses.gla.ac.uk/id/eprint/77572