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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:233163 |
| Date | January 1983 |
| Creators | Stark, William Marshall |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/4195/ |
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