Canadensolide and Other Metabolites of Pencillium canadense

Roy, Thomas Paterson (1970) Canadensolide and Other Metabolites of Pencillium canadense. PhD thesis, University of Glasgow.

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This thesis is mainly concerned with the elucidation of the structure and of the relative and absolute stereochemistry of the antifungal bis lactone antibiotic canadensolide which is found in the culture filtrates of the fungus Penicillium canadense. This work is interlinked with structural studies on five metabolites isolated from the same source. Of these,one, the bis lactone dihydrocanadensolide, had been previously isolated. The remaining four, canadensic acid, isocanadensic acid, dihydroisocanadensic acid and hydroxyisocanadensic acid were all shown to be related monolactones. The absolute stereochemistry of the natural monolactones and of various monolactones derived from canadensolide was established using ORD and CD, and in one case (canadensic acid) by multistage degradation to (-)gamma-caprylolactone. The absolute and relative stereochemistry of canadensolide was derived from the following : chemical and spectroscopic evidence of cis fusion of the two lactone rings ; determination of the absolute configuration at C-4 by conversion to a monolactone with one asymmetric centre; elucidation of the stereochemical relationship of canadensolide and dihydrocanadensolide, including the first reproduceable conversion of the former to the latter; determination of the absolute configuration at C-3 of hydroxyisocanadensic acid; assignment of the absolute configuration at C-3 in dihydrocanadensolide following chemical conversion of hydroxyisocanadensic acid to dihydrocanadensolide. The latter reaction also established the configuration at the carbinol carbon atom (C-4) in hydroxyisocanadensic acid, the result being at variance with that predicted from application of the Horeau method. A number of degradative schemes suitable for determining the distribution of label in canadensic acid biosynthesised from radioactive precursors were studied and application of one of these gave results in accord with biosynthesis via an alkylcitric acid type of intermediate. Synthetic studies and ultraviolet spectra proved to be important in establishing the structure of a new phenolic minor metabolite isolated from the culture filtrates as 3-chlorogentisyl alcohol. Synthetic work carried out on the unusual benzoylated metabolite candipolin, previously found in the mycelium of P. canadense, has disproved a peptide like structure and shown it to be N-benzoyl-L-phenylalanine N-benzoyl-L-phenylalaninyl estei.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1970
Depositing User: Enlighten Team
Unique ID: glathesis:1970-78552
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 28 Feb 2020 12:09
Last Modified: 28 Feb 2020 12:09

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