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  • (2019) Dobrowolski, Jeremy
    This PhD thesis describes the discovery of synthetic strategies to target novel heterocycles and fused ring systems. The primary aim of the research was to develop novel heterocycles as analogous systems to the antimalarial natural product dependensin as well as to explore the chemistry of these previously unreported classes of compounds. The secondary aim of this PhD project was to explore the chemistry and develop efficient synthetic routes to novel fused heterocyclic systems containing the benzazepine moiety. Previously, extensive research had been conducted on new antimalarial compounds, focusing on the flavonoid systems closely related to dependensin. However, analogous systems in which the heterocyclic oxygen atoms of dependensin are replaced by other heterocyclic atoms, generating the 5,6- dihydrodibenzo[b,h][1,6]naphthyridine, chromeno[4,3-b]quinoline and thiochromeno[4,3-b]quinoline derivatives, had been relatively unexplored. This thesis describes the efficient synthesis of a range of dihydrodibenzo[b,h][1,6]naphthyridine, chromeno[4,3-b]quinoline thiochromeno[4,3-b]quinoline derivatives using an inexpensive and versatile Friedlaender coupling methodology which allows for the generation of diverse analogues, related to the dependensin natural product. Additionally, a robust and simple synthetic pathway was developed to access novel fused heterocyclic ring systems via an initial addition-oxidation-ring cleavage cascade reaction under basic conditions in the presence of NaOH in DMSO to give a versatile 1,4-diketone intermediate. Subsequent cyclisation reactions gave the azepine moiety fused with either quinoline or indole ring systems with high levels of substitution possible. The synthesis of two novel classes of heterocycles, namely the dihydrobenzo[6,7]azepino[3,2-c]quinolinones and 11-phenylbenzo[6,7]azepino[3,2- b]indolones was achieved. This work considerably expands the number of examples of structures incorporating the dihydrobenzazepine scaffold. The range and diversity of the developed fused heterocyclic systems have resulted in four publications to date.