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Title: Studies on the synthesis and reactivity of potential new DNA binding/intercalating agents
Author: Melillo, Vito
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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This thesis is concerned with the synthesis and reactivity of condensed polyaza heterocycles as potential new DNA binding/intercalating agents. In particular, the use of isoxazoles as key intermediates in the synthesis of polyfunctionalised quinoline derivatives followed by the annulation of these latter derivatives is described. 1,3-Dipolar cycloaddition reactions of 2-nitrobenzonitrile N-oxide with conjugated alkynes or alkenes or its conjugate addition with activated methylene anions gave 3-(2-nitrophenyl)isoxazole derivatives. Reduction of the nitro-group and cyclisation through a suitable substituent in the 4 position of the isoxazole ring afforded functionalised isoxazoloquinoline derivatives, reductive cleavage of the isoxazole ring in which released masked ortho-amino-carbonyl functionality thus providing access to a variety of novel polyfunctionalised quinoline derivatives. Heteroannulation reactions of 4-amino-1,2-dihydro-2-oxoquinoline-3-carboxamide and of its 1-hydroxy analogue gave functionalised pyrimido[5,4-c]quinoline and 6-hydroxyprimido[5,4-c]quinoline derivatives respectively, while heterocyclisation reactions of ethyl 3-(4-amino-1,2-dihydro-2-oxoquin-3-yl)-3-oxopropionate and of its 1-hydroxy analogue afforded pyrido[3,2-c]quinoline and 6-hydroxypyrido[3,2-c]quinoline derivatives respectively. The reactivity of these potential new DNA binding/intercalating agents was also briefly examined. The nucleophilic displacement reactions of the peri substituted 4,5-dichloropyrimido[5,4-c]quinoline with a variety of mono- and dinucleophilic agents were the subject of substantial investigations yielding a variety of novel 4,5-disubstituted and 4,5-annulated pyrimido[5,4-c]quinoline derivatives. In addition, nucleophilic substitution reactions of 2,4,5-trichloropyrimido[5,4-c]quinoline and 2,4,5-trichloropyrido[3,2-c]quinoline were the subject of a brief examination in the course of which they were converted into a number of new 2,4,5-trisubstituted pyrimido[5,4-c]quinoline and pyrido[3,2-c]quinoline derivatives respectively.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available