Synthetic and biosynthetic studies of some fungal metabolites

This thesis is divided into five chapters, the first two of which are introductory. In Chapter 1 the secondary metabolism of fungi is briefly discussed with special reference to the polyketide pathway. Chapter 2 comprises a short r e v i e w of the isotopic tracer methods important in biosynthetic studies, concentrating on the use of nuclear magnetic resonance techniques.Chapter 3 concerns LL-D253α, a 4-chromanonemetabolite of Phoma pigmentivora. Spectroscopic evidence has led to a revision of the original structure; both this and the new structure have been synthesised. [2-¹⁴C]-, [1-¹³ C]-, [2-¹³C]-, [1,2-¹³C₂], [1-¹³C, ²H₃]-, [1-¹³C, 18O₂-, and [²H₃] acetates, [ 1-¹⁴C] glycollate, [U-¹⁴C]oxalate, [5-¹⁴C] - mevalonate and ¹⁸O2 gas have all been administered to P. pigmentivora. The results indicate a polyketide biogenesis for LL-D253α and a two-chain pathway has been proposed to account for the structure. A spiro-cyclopropyl intermediate formed by aryl participation is postulated to explain the unusual scrambling of carbon and hydrogen label observed in the 2-hydroxyethyl side-chain. Possible mechanisms for formation of the pyranone ring are discussed.Chapter 4 concerns meroterpenoid metabolites of Aspergillus species. The incorporations of ¹⁸0₂ gas and [1-¹³c, ¹⁸0₂]acetate into andibenin B and andilesin A, both known triprenyl-phenols of A.variecolor , suggest possible pathways for the formation of the spiro-lactone moiety of the andibenins. Incorporation of acetate oxygen into andilesin A was too low to distinguish between possible orsellinate and deoxyorsellinate intermediates.The biosynthesis of terretonin by A. terveus has been investigated. Assignment of the ¹³C n.m.r. spectrum is 13 described in detail. Incorporations of [1,2-¹³C₂]acetate and [carboxyl, 2-¹⁴C]- and [3-methyl, ²H₃]-3,5-dimethyl- orsellinates indicate a triprenyl-phenol biogenesis, contrary to previous suggestions.In Chapter 5 the incorporations of gas into tajixanthone and shamixanthone, metabolites of A. variecolor, are discussed. The results are consistent with earlier observations indicating the occurrence of free rotation of the symmetrical elem e n t of a b e n z o p h e n o n e intermediate. The principal mode of xanthone ring closure is demonstrated. Evidence that all the atmospherically-derived oxygen atoms are independently introduced is presented and a pathway via an anthraquinone intermediate is suggested