Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233163
Title: The biosynthesis of sulphur-containing dioxopiperazines
Author: Stark, William Marshall
ISNI:       0000 0001 2442 7816
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1983
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Abstract:
This thesis records an investigation into the biosynthesis of the aranotins, a group of sulphur-containing dioxopiperazine metabolites produced by the fungi Aspergillus terreus and Amauroascus aureus. A series of analogues of the known aranotin precursor, cyclo( L-phenylalanyl-L-phenylalanyl), fluorinated on one or both aromatic rings, was prepared, both unlabelled and labelled with 14C• These compounds were fed to Aspergillus terreus, as were £-, ~-, and ~-fluorophenylalanines, and their metabolism was followed by 19F n.m.r. spectroscopy of the extracts. A fluorinated bisdethiodi(methylthio)- acetylapoaranotin was isolated from cultures which had been fed DL-~-fluorophenylalanine or cyclo-(L-phenylalanyl-L-~-fluorophenylalanyl) • A new natural metabolite of A. terreus, cis-~,~'-di(methylthio)cyclo-( phenylalanyl-phenylalanyl), of unknown absolute configuration, was isolated and characterised. Several fluorinated analogues of this compound were detected spectroscopically in extracts which had been fed fluorinated precursors. cyclo-(L-Phenylalanyl-L-~-fluorophenylalanyl), stereospecifically monodeuteriated at the methylene group of the E-fluorophenylalanyl residue, was fed to A. terreus, and it was shown that neither the 3Rnor the 3S-deuterium was lost obligatorily during the conversion of this compound into cis-~,~'-di(methylthio)-cyclo-(phenylalanyl-E-fluorophenylalanyl), although there was a partial loss from each position. The natural product, cis-cA,c(' -di (methylthio) -cyclo-(phenylalanylphenylalanyl), was synthesised as a racemate. The compound, labelled with 35S , was fed to A. terreus, and was not significantly incorporated into bisdethiodi(methylthio)acetylaranotin. The racemic epidisulphide, ~,~'-epidithio-cyclo-(phenylalanyl-phenylalanyl), was synthesised. This compound, doubly labelled with 3H and 35S , was fed to A. terreus, and was incorporated into acetylaranotin and bisdethiodi(methylthio)acetylaranotin, with some changes in the isotopic ratios. An "intermediate trapping" experiment confirmed the ability of the fungus to biosynthesise ~,~'-epidithio-cyclo-(phenylalanyl-phenylalanyl), of unknown absolute configuration, from L-phenylalanine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.233163  DOI: Not available
Keywords: QD Chemistry
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