Phenanthrene Synthesis and the Biosynthesis of Mollisin

Byth, Anne Marie (1989) Phenanthrene Synthesis and the Biosynthesis of Mollisin. PhD thesis, University of Glasgow.

Abstract

Mollisin (1) 4.5 is derived via the polyketide pathway in the fungus Mollisia caesia and is the only known natural product to contain an aromatic dichloroacetyl moiety. Since its discovery in 1956 several 50-54 groups have attempted to unravel the biosynthesis of mollisin because of its unique structure. The ultimate aim of the work described in this thesis was to elucidate the biogenesis of this unusual fungal metabolite and is in part a continuation of the work performed 50 by A. A. Finnie 50 in this laboratory. The Introduction gives a brief account of the polyketide pathway and discusses biological chlorination, a common in vivo modification in the biosynthesis of polyketides and other classes of metabolite. The Introduction also describes in detail the mechanism for the formation of phenanthrenes via stilbene photocyclisation. This is relevant to subsequent chapters dealing with synthetic strategies to the phenanthrene derivatives which are postulated intermediates in the biosynthesis of mollisin. Practical aspects of stilbene photocyclisations are outlined in the final section of the Introduction. The biosynthesis of mollisin is discussed in Chapter 1 and is proposed to involve chlorination and then ring degradation of a polyketide derived phenanthrene (14), (15) or (16). Chapter 1 also records the disappointing result of feeding sodium [2-H3, 1-13 C]- acetate to malt agar cultures of M. caesia during the present investigation. Thus it was proposed to study the biosynthesis of mollisin by feeding deuterium labelled phenanthrenes (14) - (16) to the fungal medium. Chapters 2, 3 and 4 describe attempts to synthesise the postulated biosynthetic intermediates. The synthesis, properties and photochemistry of ortho-halostilbenes with alpha'-acetoxy-alpha-cyano or alpha'-acetoxy-alpha-carbomethoxy substituents are recorded in Chapters 2 and 3 respectively. The evidence from the photochemical experiments indicates that an ortho-halo substituent cannot be used to regio-chemically control the cyclisation step in these systems. As outlined in Chapter 3, a significant result was the finding that the 9-carbo-methoxyl group of phenanthrene (173) can be easily removed with simultaneous hydrolysis of the 10-acetoxyl group upon treatment with aqueous base. Chapter 4 mainly deals with attempts to synthesise phenanthrene (14) using benzyl protecting groups for the phenolic substituents in the starting materials. Unfortunately, no feeding experiments employing deuterium labelled phenanthrenes were conducted. However, many interesting results were obtained in connection with the photochemical synthesis of phenanthrenes.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1989
• Depositing User: Enlighten Team
• Unique ID: glathesis:1989-77969
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 15:46
• Last Modified: 30 Jan 2020 15:46
• URI: https://theses.gla.ac.uk/id/eprint/77969