Synthesis of Diamines for Testing as Antifungal Agents

Martin, William Patrick (1993) Synthesis of Diamines for Testing as Antifungal Agents. PhD thesis, University of Glasgow.

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Polyamines are thought to be essential to all living systems. The most common of these polyamines are based on 1,4-diaminobutane (putrescine) (A). The biosynthesis of putrescine and derivatives has been widely studied in plants, animals and microorganisms. In plants, two biosynthetic pathways appear to exist, whereas in mammals and fungi only one pathway occurs. It was believed to be possible to inhibit fungal putrescine biosynthesis, whilst allowing plant putrescine biosynthesis to continue via an alternative pathway. Thus, it was considered that inhibitors of the fungal pathway to putrescine would show selective toxicity towards plant-pathogenic fungi and be non-toxic to plants. The work in this project produced a variety of putrescine analogues for testing as antifungal agents. Initial targets were straight-chain analogues of putrescine. Of the primary diamines produced, E-1,4-diaminobut-2-ene dihydrochloride (B) showed most widespread antifungal activity. A general trend of increasing activity with increasing alkyl substitution on the amino group of compounds of this type was observed with the synthesis and testing of E-1,4-bis(alkylamino)but-2-enes and 3-1,4-bis(dialkylamino)but-2-enes. In particular, 3'-1,4-bis(diethylamino)but-2-ene dihydrochloride (C) showed high activity against powdery mildew. The synthetic methodology developed in the early targets was applied to the synthesis of several cyclic 1,4-diamines. In this range, high antifungal activity was seen with 1,2-bis(aminomethyl)-4,5-dimethylcyclohexa-1,4-diene dihydrochloride (D) and trans-A,5-bis(aminomethyl)-1,2-dimethylcyclohexene dihydrochloride (E). Some work was also carried out towards the synthesis of heterocyclic analogues of putrescine and also on alternative routes to the 1,4-diamine functionality. The ideas behind these schemes generate further possibilities for development of other antifungal and biologically active agents.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: David Robins
Keywords: Organic chemistry, Pharmacology
Date of Award: 1993
Depositing User: Enlighten Team
Unique ID: glathesis:1993-74898
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 27 Sep 2019 15:27
Last Modified: 27 Sep 2019 15:27

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