The research presented in this study demonstrates the critical role that organic synthesis plays in natural product chemistry. The biological activity demonstrated by 2-methyl-6-(3-methyl-2- butenyl)benzo-1,4-quinone prompted an investigation into the synthesis of this compound. This natural product showed significant activity against Staphylococcus epidermidis. Therefore the aim of this study was to synthesise 2-methyl-6-(3-methyl-2-butenyl)benzo-1,4- quinone and structural analogues. The regioselective synthetic route formulated for the synthesis of 2-methyl-6-(3-methyl-2- butenyl)benzo-1,4-quinone involved five steps. Different strategies towards the synthesis of this compound were investigated. The regioselective C-alkylation step was proving to be the most challenging. The synthetic strategies investigated included carbon alkylation of a phenoxide, directed-o-metallation, metal-halogen exchange and copper(II) Grignard-type metal halogen exchange. Problems were encountered with regioselectivity when carbon alkylation of a phenoxide was employed for the o-prenylation of o-cresol. The C-prenylated isomer was formed along with the O-prenylated isomer. When the reaction temperature was lowered, the yield of the desired C-prenylated isomer improved, whereas the yield of O-prenylated isomer declined. Although the reaction was performed under different conditions, the formation of the O-prenylated isomer could not be prevented. Therefore, another synthetic strategy was considered. The directed-o-metallation reaction was subsequently employed because of the associated regioselectivity. Unfortunately the desired product was not obtained when this method was employed. The reaction was attempted using different conditions, but the product could not be isolated. Since the directed-o-metallation protocol did not yield the desired results, another method was considered. Therefore, a metal-halogen exchange reaction was employed. The metal-halogen exchange transformation was preceded by the preparation of the o-brominated precursor. Regioselectivity-related problems were initially encountered during the synthesis of the obrominated precursor. The o-brominated isomer was formed in a 1:1 ratio with the pbrominated isomer. Further investigation led to a synthetic protocol that afforded the desired o-brominated isomer in a better yield. The metal-halogen exchange transformation was subsequently attempted, but the product was obtained in an unsatisfactory yield. Therefore, another method was employed in an effort to achieve regioselective C-alkylation with a better yield. Copper(II) Grignard-type metal-halogen exchange was successfully employed to achieve regioselective C-alkylation in good yield. The subsequent step was the deprotection, although problems were encountered, it was eventually achieved. The final step was the oxidation to obtain the desired compound, 2-methyl-6-(3-methyl-2-butenyl)benzo-1,4- quinone. The same procedure was successfully applied in the synthesis of structural analogues 2-isopentyl-6-methylbenzo-1,4-quinone, 2-(3,7-dimethylocta-2,6-dienyl)-6-methyl-1,4- benzoquinone and 2-(3,7-dimethyl-octyl)-6-methyl-1,4-benzoquinone. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.

Throughout the history of mankind, many infectious diseases have been treated with plant extracts. Venereal infections are one such group and are regarded as conditions that are highly responsive to traditional treatment. Aqueous, ethanol and ethyl acetate extracts of 13 plants used in South Africa for the treatment of venereal diseases were screened for in vitro antibacterial, antifungal, mutagenic and antimutagenic activities. Antibacterial activity was evaluated using the disc-diffusion and microdilution assays to determine the minimal inhibitory concentration (MIC) values of the extracts. The extracts were tested against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, and the Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae. Among the plants tested, Gunnera perpensa, Harpephyllum caffrum, Hypoxis latifolia and Ledebouria ovatifolia showed the best antibacterial activity. The aqueous rhizome extract of Gunnera perpensa displayed good activity against Gram-negative bacteria with an MIC value of 0.78 mg/ml, and against S. aureus (0.78 mg/ml). Aqueous and ethanol extracts of H. caffrum bark were active against both Gram-positive and Gram-negative bacteria. Hypoxis latifolia aqueous corm extracts exhibited very good MIC values against K. pneumoniae (0.78 mg/ml), E. coli and S. aureus (1.56 mg/ml). Ethanol and ethyl acetate bulb extracts of Ledebouria ovatifolia displayed good activity against Bacillus subtilis bacteria with MIC values of 0.78 mg/ml and 0.39 mg/ml respectively. Antifungal activity was evaluated using the microdilution bioassay. Good activity was shown by the ethanolic bark extracts of Bersama lucens and Harpephyllum caffrum against Candida albicans. Only in the case of Harpephyllum caffrum did aqueous extracts have activity against Candida albicans. In the Ames test, all plant extracts showed a negative genotoxic response except for ethanol and ethyl acetate bulb extracts of Cyrtanthus obliquus which induced mutations in TA98. Moderate antimutagenic activity was observed with the ethyl acetate extract of G. perpensa and the ethanolic extract of H. latifolia. High antibacterial and antifungal activity detected with Harpephyllum caffrum bark extracts resulted in an investigation on seasonal and geographical variation of this inhibitory activity. Seasonal variation in antibacterial and antifungal activities was investigated in order to determine the best collection time to ensure potential high medicinal activity in plant preparations. The highest inhibitory activity was detected with plant material collected in June and December 2003, with a decline in activity when collections were made in September 2004. The chemical profiles of TLC chromatograms were compared and little variation was found, particularly in the case of plant material obtained from the Botanic Garden of the University of KwaZulu-Natal and a 'Muthi' Shop in Pietermaritzburg. Identification of active compounds from G. perpensa and H. caffrum was not successful due to insufficient amounts of isolated fractions. / Thesis (Ph.D.)-University of KwaZulu-Natal, 2006.

D. Tech. (Department of Chemistry, Faculty of Applied and Computer Sciences)|, Vaal University of Technology. / Medicinal plants provide valuable alternative sources of drugs and drug discovery because many have been used in traditional practices for centuries to manage or treat various forms of ailments. The aim of this study was to evaluate the biological activities of nine medicinal plants used by Zulus in Mabandla village, KwaZulu-Natal province, South Africa to treat inflammation and to isolate selected active compounds against studied pathogens from Alepidea amatymbica and Pomaria sandersonii. The plants were selected on the basis of an ethnobotanical survey based on questionnaire response and verbal interviews that were conducted in Mabandla village with the local traditional healers and herbalists. The isolation of compounds from Alepidea amatymbica and Pomaria sandersonii was based on the bioassay based study which was carried out in this study. Bioassay guided study involving in vitro anti-inflammatory measurement using soya bean derived 15 Lipoxygenase, free radical scavenging capacity against the ABTS●+ radical cation and DPPH● radicals; antimicrobial and bioautography assays against Staphylococcus aureus, ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Enterococcus faecalis ATCC 29212, Escherichia coli, ATCC25922, Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus were carried out using the plants extracts, fractions and pure compounds. Isolation of compounds displaying biological activity was carried out by using open column chromatography and preparative thin layer chromatography (PTLC). The compounds were characterised by use of Nuclear Magnetic resonance, (NMR) and Mass Spectrometry (MS). The DPPH sprayed TLC showed that all the nine plants contained antioxidants. Most of which were contained in polar fractions of acetone and methanol. Results of the assays displayed a range of biological activities comparable to the positive controls used for each assay. DPPH● scavenging displayed EC50 values ranging between 1.008 and 467 Kg/ml. The highest activity was observed with the methanol fraction of Berkheya setifera with an EC50 value of 1.008 Kg/ml followed by the crude extract of Gunnera perpensa with EC50 value of 1.069 Kg/ml. Carissa bispinosa hexane fraction had the lowest activity of 467.7 Kg/ml. The Pomaria sandersonii DCM extract had the highest ABTS●+ radical scavenging activity by Pomaria sandersonii DCM extract, (1.273 Kg/ml) for the ethyl acetate, (5.973 Kg/ml) while the hexane fraction from Eucomis autumnalis had the lowest activity (929.4 Kg/ml). The activity of Pomaria sandersonii extracts and fractions demonstrated that the plant contains antioxidants that react with both DPPH and ABTS radicals although higher activities were shown by ABTS as displayed by the lower EC50 values. All the crude fractions and extracts had high to moderate antibacterial activities (20-625 Kg/ml) and anti-fungal activities (20-2500 Kg /ml). Pomaria sandersonii crude and fractions had the highest antimicrobial activity compared to other plants. Some MIC values for P. sandersonii dichloromethane and ethyl acetate fractions (80 Kg/ml in each case) compared well with gentamycin (4 Kg/ml) since they showed same values against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudonomus aeruginosa. The dichloromethane, acetone and methanol fractions were also active (20 Kg/ml) against both Candida albicans and Aspergillus fumigatus. Inhibition of pathogen growth demonstrated by the polar fractions of the studied plants suggested that some of the active compounds would be soluble in water. A total of seven compounds were isolated from Alepidea amatymbica and Pomaria sandersonii. We propose three were new compounds after considering literature search involving closely related research to this investigation. These were two diterpenes from Alepidea amatymbica, namely, 14-acetoxo-12-oxokaur-16-en-19-oic acid labelled as 0657 and 16-hydroxy-kaur-6-en-19-oic acid given the label 06-2 in this study. The third suspected new compound is the chalcone dimer, which is referred to as EM86 in this study from Pomaria sandersonii. EM80-2 was obtained as a mixture of the cis and trans of 2’, 4, 4,’-trihydroxychalcone or 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one, from Pomaria sandersonii. The three diterpenes, 14-acetoxokaur-16-en-19-oic acid (0652), 13-hydroxy-16-kauren-19-oic acid (06B) and 14-oxokaur-16-en-19-oic acid (06431) were isolated from Alepidea amatymbica for the first time. Isolated compounds were further tested as individual compounds and results showed that 16-hydroxy-kaur-6-en-19-oic acid (06-2) had weak activity against tested bacteria and fungi with the MIC: Staphylococcus aureus (320 Kg/ml) and Candida albicans, (320 Kg/ml). On the other hand 13-hydroxy-kaur-16-en-19-oic acid (06B) was more active against, Staphylococcus aureus (160 Kg/ml) and Aspergillus fumigatus (40 Kg/ml). The yellow compound that was isolated from Pomaria sandersonii, 1-(2, 4-ihydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one was antimicrobial with the following MICs: Candida albicans: 80 Kg/ml; Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus: 160 Kg/ml and Aspergillus fumigatus: 625 Kg/ml. There were two mixtures referred to as EM 49 and EM 77 from Pomaria sandersonii which were difficult to purify but had anti-microbial inhibitory activities worth reporting. EM49 had MIC against Candida albicans of: 160μg/ml; Pseudomonas aeruginosa: 320 Kg/ml, Escherichia coli: 80μg/ml, Enterococcus faecalis 80μg/ml, and Staphylococcus aureus: 80μg/ml and Aspergillus fumigatus: 320μg/ml. EM 77 had MIC against Escherichia coli: 80 Kg/ml and Cryptococcus neoformans: 80μg/ml. Further work on their purification need to be done since in this research we are just reporting on their high MIC activities. The medicinal plants used to treat inflammation under different disease conditions in the Zulu community of Mabandla village, Kwa-Zulu Natal, South Africa have some relevant biological activities. The various antimicrobial, antioxidant and anti-inflammatory activities support the validity of their healing capacities that the traditional healers of the community claim to possess. Although there is evidence of good antimicrobial, antioxidant and anti-inflammatory activities by the crude extracts, the high levels of sucrose in P. prunelloides and glucose in G. perpensa should be borne in mind when using their decoctions in traditional medicine particularly by diabetic patients. In vitro results for the antioxidant, antinflammtory and antimicrobial activities carried out in this investigation illustrate that the plants can be a source of treatment and management for inflammation related conditions. These therefore justify their use in Zulu traditional medicine. However, in vivo assays should be carried out in order to completely validate claims by the traditional healers that they treat inflammation related conditions. / Vaal University of Technology