In the present study, a phytochemical investigation of two medicinal plants, namely, Acridocarpus natalitius and Typha capensis is presented. The roots of A. natalitius afforded a variety of pentacyclic triterpenoids, namely, friedelin [41], epi-friedelinol [42], lupeol [43] and oleanolic acid [44], including stigmasterol [45] from the hexane extract, whilst the methanolic extract produced a flavonoid, (-)-epicatechin [4] and carbohydrates which included glucose [64] and sucrose [65]. Two new bibenzyls were isolated from the hexane extract of the rhizhomes of T. capensis, namely, typharin [47] and typhaphthalide [48]. β-Sitosterol [49] was also isolated. The acetone extract afforded several flavan-3-ols which were isolated in their free phenolic form. These include, afzelechin [10], epiafzelechin [23], (+)catechin [11] and (-)-epicatechin [4]. A biological survey was carried out on the crude methanolic extract in an independent survey and a brief discussion is presented here. All the compounds were isolated using a series of chromatographic techniques and structures were elucidated by means of NMR spectroscopy, infrared spectroscopy and mass spectrometry. / Thesis (M.Sc.)-University of Durban-Westville, 2001.

The heartwoods of two species of South African Euphorbiaceae have been chemically investigated. From Cleistanthus schlechteri three new diterpenes possessing the hitherto unknown ent-isopimara-8(14),15-diene skeleton were isolated. By means of chemical and spectroscopic methods these were shown to be 3a-hydroxy-ent isopimara-8(14),15-diene, I, 3a-hydroxy-ent-isopimara- 8(14},15-dien-12-one, II, and 3a,12a-dihydroxy-ent-isopimara- 8(14),15-diene, III. A biogenetic sequence has been proposed in which it is suggested that these compounds are probably the precursors of the major diterpenoid, cleistanthol, IV, previously isolated from this source. From the second species, Spirostachys africana, a new diterpenoid seco-acid, spirostachic acid, VIII, was obtained in addition to the beyerene derivatives previously reported. Mass spectral fragmentation patterns of the seco-acid and its methyl esters proved to be useful as a diagnostic tool in structure elucidations. / Thesis (Ph.D.)-University of Natal, Durban, 1971.

No abstract available. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 2001.

Cephalotaxine is a naturally occurring alkaloid which is the structural motif of a number of compounds which have shown promising anti-cancer properties. This fact together with its relatively complex pentacyclic structure, which incorporates an azaspirocycle annular to a benzazepine moiety, has resulted in its popularity as a synthetic target. The aim of this project was to synthesise the azaspirocycle of cephalotaxine using a Noyori annulation method involving the reaction of an enamine and an a,a' -dibromo ketone in the presence of Fe2{CO)9. In the first attempt the reaction of l-benzyl-2-methylenepyrrolidine (117) with methyl 2,4-dibromo-3-oxobutanoate (116) proved to be unsuccessful, the electron withdrawing ester functionality of methyl 2,4-dibromo-3-oxobutanoate (116) being unable to stabilise the intermediates formed during the reaction and thus resulting in its failure. Reaction of l-benzyl-2-methylenepyrrolidine (117) and 2,4-dibromo-3-pentanone (114) resulted in the formation of an azaspirocycle though in an extremely poor yield and the reaction was deemed inefficient for the synthesis of the cephalotaxine spirocycle. Finally, reaction of 2-(l-benzyl-2-pyrrolidinylidene)acetonitrile (129) and 2,4-dibromo-3-pentanone (114) resulted in the successful synthesis of a novel azaspirocycle. The product, l-benzyl-7,9-dimethyl-8-oxo-1-azaspiro[4.4]nonane-6-carbonitrile (130), contained four stereogenic centres and one of the diastereomers was successfully crystallised out. The X-ray structure in conjunction with NOESY NMR experiments showed the relative stereochemistry to be 5s', 6s', 7s', 9s'. Significant progress was made in the application of this methodology to the construction of the cephalotaxine pentacyclic skeleton with the synthesis of a novel lactam, 1-[2-(6-iodo-I,3-benzodioxol- 5-yl)ethyl]-2-pyrrolidinone, being achieved. In the course of this work a novel compound, 2-(6-Iodo-1 ,3-benzodioxol-5-yl)ethyl 4-methylbenzenesulfonate (98), was also synthesised and its X-ray structure revealed it to be conformationally interesting. As a result a conformation analysis study was carried out on this compound as well as 2-(6-Iodo-I,3-benzodioxol- 5-yl)ethyI 4-nitrobenzenesulfonate (15a). The Noyori annulation reaction was not implemented in the route to the basic pentacyclic structure of cephalotaxine due to time constraints, however synthesis of analogues of cephalotaxine and other alkaloids possessing azaspirocycles should now be possible based on the methodology developed in this project. / Thesis (M.Sc.)-University of Natal Pietermaritzburg, 2001.

Cylindricines A-K [1-11], lepadifonnine [12] and fasicularin [13] are tricyclic ascidian alkaloids exhibiting the perhydropyrrolo[2,1 :j]quinoline and perhydropyrido[2,1-j]quinoline ring systems. The structural features and biological activity of these alkaloids make them ideal targets for total synthesis. The first aim of this project was to construct the azabicycles [111] and [112] that resemble the spirocyclic core of these alkaloids. The synthesis began with the C ring intact and the attempted construction of the B ring using Diels-Alder methodology. A key step was the Eschenmoser coupling reaction between thiolactams [105] and [106] to give the vinylogous amides [107] and [108]. All attempts to convert the vinylogous amides to the corresponding dienes proved to be unsuccessful, due to the fact that the preferred site for deprotonation was ~ to nitrogen and not a to the carbonyl group. Due to time constraints we moved to our second aim, the enantioselective synthesis of the B and C rings offasicularin [13]. Significant progress was made towards our second goal. (5S)-5-Hydroxytetrahydro2(lH)pyridinone [127], which represents the C ring of fasicularin, was successfully synthesized in 5 steps from L-glutamic acid [113]. This lactam was O-protected with tertbutyldiphenylsilyl group to afford (5S)-5-tert-butyldiphenylsilyloxy-2-piperidinone [114]. Thionation of lactam [114] gave the thiolactam [160]. Conjugate addition of this thiolactam to methyl acrylate gave methyl 3-[(5S)-5- {[tert-butyl(diphenyl)silyl]oxy}-2-thioxotetrahydro1(2H)-pyridinyl ]propanoate [163], which underwent a Eschenmoser coupling reaction with bromoacetone to gIve methyl 3-[(5S)-5-{ [tert-butyl(diphenyl)-silyl]oxy} 2-[(£)-2oxopropylidine] tetrahydro-2(1H)-pyridinyl]propanoate [164]. Unfortunately conversion of [164] into the corresponding diene using KHMDS and TBSCI was unsuccessful. The reaction conditions caused the cleavage of the methyl acrylate protecting group on nitrogen, affording the secondary E-vinylogous amide [167]. This constituted an important serendipitous discovery - methyl acrylate can be used to protect the nitrogen atom of enaminones and can be removed by KHMDS to access secondary E-enaminones that are otherwise difficult to synthesise. Another route pursued was to introduce the hexyl chain in the A ring of fasicularin by means of an SN2 reaction between lactam [114] and mesylate [116]. The stereodefined (lR)1-(2-{[tert-butyl-(dimethyl)sily]oxy}ethyl)heptyl methanesulfonate [116] was successfully x synthesized in 5 steps from l-octyne [115]. Unfortunately the subsequent SN2 reaction with lactam [114] failed when we using t-BuOK and THF and time constraints prevented us from attempting this coupling reaction using alternative conditions. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 2002.

We have developed a new coarsening theory that more completely describes grain growth of a system of anisotropic particles such as completely faceted crystals by Ostwald ripening. Our model takes the anisotropy of surface energies on dissimilar facets into account, and the particle sizes are described by a distribution function. The theory is applied to study the coarsening of ,B-silicon nitride in a liquid medium due to the anisotropic growth of grains in different crystallographic directions. A model of the growth of silicon nitride grains is obtained based on the numerical solution of the equations of the new theory. Computer experiments are performed to determine how the distribution function evolves, to investigate the influence of various parameters such as diffusion and interfacial reaction constants on grain growth and to extract grain growth exponents from this model in order to determine the growth mechanisms that are responsible for the anisotropic growth behaviour. Only preliminary numerical results are available thus far due to 1/r instabilities that occur in the theory as r → 0. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 2002.

This study comprised the synthesis and characterization of select phosphine ligands and their complexation to gold(I). An initial approach was the reaction between Ph2PCl in "wet" organic solvent and [ClAu(tht)] (tht = tetrahydrothiophene) which led to the complex [ClAu{Ph2P(OH)}], 1, which was the second polymorph of this complex based on solid state Xray crystallographic studies. Related to the Ph2PCl precursor, the study refocused on the preparation of the ligand bis(diphenylphosphino)acetonitrile, (PPh2)2CHCN, ("dppm-CN"), 2, obtained from a modified literature method. Ligand 2 underwent a facile reaction with either [ClAu(tht)] or [(C6F5)Au(tht)] (molar ratio 1:2) to yield new open-ended dinuclear gold(I) complexes [(ClAu)2(dppm-CN)], 3, and [(C6F5Au)2(dppm-CN)], 4, respectively, both in satisfactory yield. Ligand 2 can also be deprotonated to form the anion [(PPh2)2CCN]¯ which reacted with [AuCl(tht)] (molar ratio 1:1) to form the neutral cyclic dinuclear gold(I) complex [Au2{(PPh2)2CCN}2], 5. The anion [(PPh2)2CCN··· showed unexpected reactivity behaviour toward mono- or bis(phosphine) gold(I) chloride complexes that led to the cleavage and formation of new Au-P bonds. Complexes 1, 3, 4, 5 were all subjected to a single crystal X-ray studies. Complex 1 has a central intermolecular Au···Au interaction of 3.0375(2) Å, and peripheral hydrogen bonding (O-H···Cl) within the structure. Complex 3 displays an intramolecular Au···Au interaction of 3.1669(4) Å, but no other intermolecular interactions. The structure of complex 4 reveals a side-by-side "dimer of dimers" structural motif in the solid state and represents a new type of system. Complex 4 contains intramolecular Au· · ·Au interactions alternating between 3.0902(7) Å and 3.0809(6) Å, and an intermolecular Au· · ·Au interaction of 3.592 Å. The next dimeric unit along the virtual 1D chain is more than 6 Å away. Complex 5 has an intramolecular Au···Au separation of 2.8650(4) Å and no intermolecular interactions. The C≡N bond in 5 is 1.160(7)° and is longer relative to the C≡N bond in complexes 3 and 4. The new complexes were further investigated by elemental analyses, mass spectrometry, 1H and 31P solution NMR, and FT-IR. The luminescence properties of the complexes was investigated in the solid state. Results showed 3 to be non- or very weakly emissive at room-temperature, the emission of 4 seems to be quenched by the C6F5 group at room temperature and qualitative results for 5 showed luminescence both at room temperature and at 77K. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

Layered double hydroxides (LDHs) or hydrotalcite-like compounds (HTLcs) are classified as anionic clays in which their structure is based upon brucite and are represented by the following general chemical formula: [MII1-xMIII x(OH)2]x+(An-)x/y.yH2O where MII and MIII represent various possible divalent cations, e.g., Mg2+, Zn2+, Ni2+, Co2+ and Fe2+ and trivalent cations, e.g., Al3+, Fe3+ and Cr3+ respectively. The value x is equal to the stoichiometric ratio of MIII/(MII+MIII) and An- represents exchangeable anions such as CO32-, Cl- and SO42-. It is these exchangeable interlayer anions, which make layered double hydroxide compounds excellent carriers of negatively charged or anionic containing biomolecules, such as DNA and hence can be exploited in their use in gene therapy. In this study, a variety of Mg-Al hydrotalcites (HTs), Zn-Al, Zn-Fe and Mg-Fe LDHs were synthesized using co-precipitation. The synthesized compounds were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, Inductively coupled plasma-optical emission spectroscopy (ICP-OES), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM) and Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX). XRD patterns for the synthesized HTs and LDHs exhibited characteristic features indicative of an ordered layered material. Elemental analysis of the compounds revealed a measured value of x in the range of 0.25-0.33 for Mg-Al HTs and Zn-Fe LDHs, 0.11-0.16 for Zn-Al LDHs and 0.55-0.58 for Mg-Fe LDHs. FTIR and Raman spectroscopy confirmed the presence of characteristic functional groups and interlayer anions. From electron microscopy, the compounds exhibited classical morphologies typical of HT and LDH compounds and had a lateral size range of 200-300 nm. These compounds were studied in their ability to bind DNA with the use of a gel retardation or band shift assay. This assay confirmed that these compounds are indeed able to bind DNA. The binding mechanism of DNA to the HT and LDH compounds was evaluated and plausible mechanisms were proposed. Furthermore, nuclease digestion assays were carried out in order to evaluate the potential protecting ability that these compounds afford towards the bound DNA in the presence of serum. It was observed that all compounds protected most of the bound DNA. The cytotoxicity of the compounds was evaluated in the HEK293, HepG2 and HeLa mammalian cell lines using the MTS (3-(4,5-dimethylthiazol-2yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salts) assay with a concentration range of 20-100 μg of respective HT/LDH compound. For most of the compounds, cell viability was observed in excess of 80 %. Finally, transfection studies were carried out utilizing green fluorescent protein (GFP) analysis and luciferase gene expression using the same mammalian cells in culture. It was noted that all HTs and LDHs were able to release DNA in a controlled prolonged manner over a period of three days. Green fluorescent protein gene expression commenced after 27 hours and reached a maximum at 72 hours. Efficient luciferase gene expression was observed with luciferase activities for DNA: HTs ranging from 0.05 x 106 - 2.0 x 106 RLU / mg protein and DNA: LDHs ranging from 0.05 x 106 - 16.7 x 106 RLU / mg protein. Highest luciferase activity was recorded as 16.7 x 106 RLU / mg protein. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

Three diterpenes of the abietane class, 7b-acetoxy-6b-hydroxyroyleanone (I), 6b,7b- dihydroxyroyleanone (II) and ent-pimara-8(14),15-diene-3b,11a-diol (III) and three triterpenes, 2a,3a,19 -trihydroxyurs-12-en-28-oic acid (IV), stigmasterol (V) and lupeol (VI) were isolated from the stem and leaf material of Plectranthus hadiensis. The structures of the compounds were elucidated using 2D NMR spectroscopy and Mass spectrometry. All six compounds have been isolated previously, but this is the first occurrence of compounds III-VI in Plectranthus hadiensis. This is also the first report of the isolation of a pimarene from Plectranthus, which provides a biochemical link to other genera in the family Lamiaceae where this class of compounds exist. Compounds I to IV were tested for their antibacterial activity against Enterococcus faecalis and Pseudomonas aeruginosa as well as their anticancer activity against breast (MCF-7), renal (TK- 10) and melanoma (UACC-62) cell lines. Compounds I and II exhibited good antibacterial activity against Enterococcus faecalis and Pseudomonas aeruginosa and although the entpimara- 8(14),15-diene-3 ,11 -diol (III), was inactive against E. faecalis, it was very active against P. aeruginosa. Compound IV, the triterpenoid, was structurally different to I-III and did not show any anti-bacterial activity. Compounds I-III were weakly active toward the cancerous renal (TK-10), melanoma (UACC-62) and breast (MCF-7) cell lines, while IV was inactive in all of the cell lines. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

The purpose of this investigation was to study the effect of the carbamate group on the reactions and reactivity of substituted 1,1-diphenylmethane and a,ro-diphenyl allylic compounds. A series of carbamates were prepared and reacted with a variety of electrophiles and nucleophiles. l-(O-N,N-dimethylcarbamoyloxy)-l,l-diphenylmethane (i) reacted with a variety of electrophiles to afford a-substituted carbamate products (H). Reactions of allylic carbamates with electrophiles proceed with substitution at the carbon atom a or y to the carbamate. 1-(O-N,N-diethylcarbamoyloxy)-1,3-diphenyl-2-propene (iii) only reacted with methyl iodide to afford the y-substituted product (iv). Reactions of 1-(O-N,N-diethylcarbamoyloxy)-l ,5-diphenyl-2,4-pentadiene (v) with electrophiles were all unsuccessful. Nucleophilic substitution reactions were performed with carbamates (i), (iii) and (v). No success was achieved in the reactions of (i) with nucleophiles. Carbamates (iii) and (v) reacted with a few oxygen nucleophiles to afford allylic ethers with simultaneous elimination of the carbamate group. Several properties ofterminal-diphenyl carbamates have been revealed: (a) Benzylic carbamate (i) reacted successfully with a variety of electrophiles. Nucleophilic substitution is not favoured with the benzylic carbamate. This indicates that SN2 elimination of the carbamate does not occur in this molecule. (b) Allylic carbamate (iii) only reacts with methyl iodide indicating that the bulk of the diethyl substituents on the carbamate group, the bulk of the incoming electrophile and the size of the phenyl groups are fundamental to the success of reaction. Methylation occurred only at the y-position. (c) Conjugated allylic carbamate (v) did not react with any electrophiles, suggesting that, in addition to the steric factors, the stability offered in the retention of conjugation in the molecule prevented the formation of the electrophilic substitution products. (d) Unsymmetrical allylic carbamates (iii) and (v), in which the carbamate occupies a benzylic position, are more stable than symmetrical allylic carbamates (vi) and (vii) which decompose to the corresponding alcohol. (e) Nucleophilic substitution of (iii) and (v) occurred with SN2' elimination of the carbamate group, the reaction proceeding in a way which faciliates the formation of the most conjugated product possible. Nucleophilic substitution of (iii) with the phenoxide anion resulted in the allyl aryl ether (viii). Several attempts were made to promote the Claisen rearrangement to afford the allylic phenol (ix) but without success. Exploitation of the migrational ability and the leaving group ability of the carbamate moiety were extended to the synthesis of /13-flavene (xi) from allylic alcohol (x). Several attempts were made to synthesise (x) via the Aldol condensation and Grignard reactions. The synthesis of (xi) was hindered by the failure to produce allylic alcohol (x). During the course of these investigations an unexpected decomposition reaction was discovered. The purification by distillation of allylic carbamate (xii) afforded allylic amine (xiii) in quantitative yield. The driving force for the reaction is the intramolecular SN2' elimination of the carbamate with the simultaneous loss of carbon dioxide. This reaction may have scope in the synthesis of allylic amines. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1995.