An Investigation Into the Biosynthesis of Terrein

McCusker, Michelle Elizabeth (1992) An Investigation Into the Biosynthesis of Terrein. PhD thesis, University of Glasgow.

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Abstract

An investigation has been carried out into the nature of the biosynthesis and the metabolites involved in the production of the natural product, terrein. Terrein, a metabolite of the fungus Aspergillus terreus has been previously shown to be of polyketide origin. It seems likely that terrein may be derived by way of an aromatic intermediate with subsequent oxidative cleavage of the aromatic ring to a five-membered ring. It is the nature of this ring contraction which is of primary interest. Also under investigation was the stereochemistry of the elimination process leading to the propenyl side chain of terrein. 3,4-Dihydro-6,8-dihydroxy-3-methylisocoumarin is already known to be an intermediate on the pathway to terrein and this fact was utilised in the investigation of the side chain modification of terrein. The two deuterium labelled isocoumarins [4,alpha,alpha,alpha -2H4]-3,4-dihydro-6,8-dihydroxy-3-methylisocoumarin and [3,4-2H2] -3,4-dihydro-6,8-dihydroxy-3-methylisocoumarin were synthesised and fed to Aspergillus terreus. Results showed that both were incorporated to some extent but some partial degradation of the isocoumarins to acetate was also observed. In the ring contraction step it is known that C-7 of the isocoumarin is lost. Thus a possible intermediate containing an oxygenated carbon at C-7 was examined. Several synthetic routes to 3,4-dihydro- 6,7,8-trihydroxy-3-methylisocoumarin were investigated since the synthesis used for the 6,8-dihydroxyisocoumarin was not applicable in this case. The intermediacy of 2,3,5-trihydroxyphenylpropene was also explored. Two different synthetic strategies to this compound were employed, one involving the condensation of a phosphonic acid bisamide with an appropriate ester derivative, the other making use of the ortho-Claisen rearrangement.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1992
Depositing User: Enlighten Team
Unique ID: glathesis:1992-78393
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:29
Last Modified: 30 Jan 2020 15:29
URI: http://theses.gla.ac.uk/id/eprint/78393

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