Studies of the chemical and biosynthetic interrelationships of alternariol.

The first chapter consists of a review of the background literature and provides a general introduction to the current study. Various aspects of the chemistry of alternariol and the biosynthetic interrelationships of this key Alternaria alternata product to other phenolic metabolites of this fungus, are described in the remaining two chapters. The principal findings are summarised below: (i) A conspicuous feature of alternariol and its derivatives is the intense fluorescence associated with the tricyclic ring system. This fluorescence is lost on opening the 6-lactone ring which under acidic conditions undergoes spontaneous recyclisation. The rate of lactone formation was found to be highly dependent upon the extent of methylation of the phenolic hydroxyl substituents, particularly that present at C(4'). (ii) The chemistry of various bromo derivatives of alternariol and its methyl ethers have been investigated. (iii) Thin layer chromatographic and autoradiographic procedures were developed for the analysis of biosynthetically-derived 14 C -labelled metabolites of A. alternata. Eight strains of the species, while differing quantitatively in their ability to produce alternariol and its congeners, were shown to be qualitatively similar. A corresponding observation of the metabolism of the botrallin-producing mould Botrytis allii indicated a close taxonomic relationship between these two genera. (iv) Two low alternariol-yielding strains of A. alternata were observed to metabolise alternariol when added to growing cultures. This effect was more pronounced on feeding the acidic form obtained on hydrolysis of the delta-lactone to the dehydroaltenusin-producing strain (T139) and led to considerably enhanced yields of this metabolite, in addition to a significant increase in mycelial growth. (v) An autoradiographic examination of the products formed on incubating the lactonic acid form of (O[14]CH[3])-alternariol monomethyl ether with mycelia of A. alternata T139, clearly demonstrated the incorporation of this precursor into dehydroaltenus in. (vi) In contrast to the stimulation of mycelial growth by alternariol and its monomethyl ether, the di and trimethyl ethers were shown to exert a marked inhibitory effect.