Browsing by Author "Swigelaar, Wendell Peter"

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    The synthesis of 3-allyl-4-ethyl-2- (1'-hydroxyethyl)-1-methoxynaphthalene and its behaviour towards base- and palladium-promoted cyclisation under aerobic and anaerobic conditions
    (University of the Western Cape, 2005) Swigelaar, Wendell Peter; Green, I. R.; Giles, R.G.F.; Dept. of Chemistry; Faculty of Science
    Over the years, Giles and co-workers have established that, upon treatment with potassium tert-butoxide, tetra-substituted naphthalenes undergo cyclisations to afford naphthopyrans. It was suggested that these base-induced cyclisations was as a result of the reacting centers being forced into close proximity as a consequence of steric crowding. This thesis describes the synthesis of 3-allyl-4-ethyl-2-(1′-hydroxyethyl)-1-methoxy-naphthalene 177 and its behaviour towards Pd(0) and potassium tert-butoxide under aerobic and anaerobic conditions, to verify whether the base-promoted cyclisations are indeed caused by the steric influences of the substituents. Two synthetic routes were attempted in the synthesis of the target naphthalene 177. The first of these attempted routes involved the conversion of 2-acetyl-4-hydroxy-1-methoxynaphthalene 182 into 2-acetyl-1-methoxy-4-trifluoromethanesulphonyloxy-naphthalene 191 and subsequently into 2-acetyl-4-ethyl-1-methoxynaphthalene 192 via Stille coupling. However, the subsequent Snieckus ortho-directed metalation reactions on the reduced 4-ethyl-2-(1′-hydroxyethyl)-1-methoxynaphthalene 193, and analogues of it, to afford naphthalene 177 were unsuccessful. The second route entailed a Claisen rearrangement of the tri-substituted 2-acetyl-4-allyloxy-1-methoxynaphthalene 209 to afford the unstable tetra-substituted 2-acetyl-3-allyl-4-hydroxy-1-methoxynaphthalene 210, which was immediately converted into the corresponding 2-acetyl-3-allyl-1-methoxy trifluoromethanesulpholnyloxynaphthalene 211. Stille coupling of the triflate 211 gave the 2-acetyl-3-allyl-4-ethyl-1-methoxy-naphthalene 212, which was subsequently reduced to the target naphthalene alcohol 177.The base-induced cyclisation studies performed on naphthalene 177, confirmed the hypothesis that these cyclisations of terta-substituted naphthalenes are indeed as a result of steric crowding.
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    The Synthesis of Biaxial Naphthoquinones and an Initial Investigation regarding their Potential as anti- Mycobacterium tuberculosis and Apoptotic Agents
    (University of the Western Cape, 2009) Swigelaar, Wendell Peter; Green, Ivan R.
    Tuberculosis and cancer are amongst the most devastating diseases affecting the world today, especially Africa and other less developed countries. Both diseases have the ability to develop resistance against drugs being used as treatment regimes and therefore the search for effective novel drugs remains an ongoing challenge. Diospyrin and its monomer 7-methyljuglone, both naturally occurring quinones, and their synthetic derivatives have been shown to exhibit significant antimycobacterial and anti-tumour activity. The present study focuses on the synthesis of new compounds of similar structures to that of the lead compounds diospyrin and 7-methyljuglone, and their evaluation as potential antimycobacterial and anti-cancer agents via apoptosis. Three methoxynaphthoquinones were synthesized and coupled to several commercially available boronic acids using the Suzuki methodology. Eight compounds were evaluated against a drug susceptible strain, H37Rv of Mycobacterium tuberculosis, using the BACTEC method. Results indicate that the presence of an hydroxyl group peri to the quinone carbonyl moiety is crucial for these quinonoidal compounds to be effective as anti-TB agents, since their methyl ether analogues had little effect on the growth rate of the bacteria. Substituents, capable of donating electrons through a resonance electron effect to the carbonyl group, peri to the methoxy group, also enhance activity of these molecules. Several of the synthesized compounds were screened for their ability to induce apoptosis in five human cancer cell lines viz.,Hl57,Hek239T, HeLa, Jurkat, MCF-7 and two non cancerous cell lines viz., CHO (animal) and KMST-6 (human). The methods employed to assess the pro-apoptotic potential of the compounds were APOPercentagerM and DNA fragmentation. The APOPercentagerM assay showed that the activity of the compounds is concentration dependent and also revealed that in addition to the redox ability of the quinone carbonyl groups, the peri methoxy or hydroxyl group also plays a role in the apoptotic activity. An independent evaluation, the DNA fragmentation test, confirmed both a degree of selectivity viz, being not too active against non-cancerous cell lines on the one hand whereas on the other having a high apoptotic potential against all five of the cancer cell lines evaluated.