The aim of the project was to synthesize warburganal, a natural product isolated from the Warburgia plants native to Venda, known as a potent molluscicide, in a new, cheaper and more efficient way to be used in the ongoing war against bilharzia. A synthetic pathway beginning with geraniol as the starting material was planned to afford a 7-step route. The first step involved the substitution of a bromine group for a hydroxyl group. Geranyl bromide underwent an alkylation step with the dianion of methyl acetoacetate to afford methyl 3-oxo-7, II-dimethyldodeca-6E, IO-dienoate. The . next Lewis acid-catalyzed step involved formation of the bicyclic decalin ring system, methyl (IR* ,4aS*,8aS*)-2-oxo-5,5,8a-trimethyldecahydronaphthalene-I-carboxylate. The next step was to add a hydroxyl group alpha to the ester, the a-OH being vitally important to the biological activity of warburganal. This step proved to be unsuccessful with the methodology used. A change in tactics was obviously required and initially protection of the ketone as an acetal was attempted. Instead of the expected acetal product, an epimer of the decalin structure above, namely, methyl (IS*,4aS*,8aS*)-2-oxo-5,5,8a-trimethyldecahydronaphthalene-I-carboxylate was isolated. This epimer seems to form under acidic as well as basic conditions and was also isolated from an a-hydroxylation reaction that employed KH and MoOPH. Most of the steps were attempted on model compounds to enable the conditions to be optimized prior to attempting the reaction on the warburganal precursor. It was soon discovered that for reasons as yet unknown, the reactions that worked on the model compounds did not always work on the warburganal precursors, although the model compounds possessed functional groups that best simulated those possessed by warburganal. The progress reported towards the synthesis of warburganal highlights the many difficulties encountered when introducing the requisite functional groups on to the decalin ring skeleton to afford warburganal i. e. the a-hydroxyl and p-aldehyde moieties and the a,p-unsaturated aldehyde. Although the planned synthetic pathway was not entirely successful, the pitfalls encountered are discussed and potential solutions are presented. A number of interesting and unexpected compounds were isolated en route and ideas are discussed that may well culminate in an efficient synthesis of warburganal. / Thesis (Chemistry)-University of Natal, Pietermaritzburg, 1998.

The aims of this study were to characterise and quantify wood extractives in E. grandis and E. nitens and determine the impact of wood extractives on pitch formation. Initially a comparison was made with individual solvent abilities to determine whether the polarity index plays a role in the amount of extracts being removed. After this different methods were used to determine the extractive amounts. These methods included hot water/ethanol-toluene, hot water/acetone and followed by acetone only. Analyses such as UV-Vis, acidolysis and HPLC were carried out to determine the presence of lignin and sugars in the extracts and sawdust respectively. Lastly GC and GC-MS was performed to characterise and quantify extractives present in the extracts from the different methods. The results showed that acetone is the preferred solvent as it removes higher amounts of extractives than ethanol-toluene. There is also a higher amount of extractives in E.grandis sawdust than in the E. nitens sawdust and pitch sample. There seems to be more fatty acids and sterols in the E. nitens sawdust sample extracted the using acetone (no hot water extraction) method while hydrocarbons are extracted more in E. grandis using the same method. It was found after GC-MS analysis that fatty acids tetradecanoic acid methyl ester and hexadecanoic acid methyl ester and hydrocarbon 1-Octadecene were common to both species. The common compounds in the pitch and sawdust of E. nitens are heptadecanoic, octadecanoic, tetradecanoic and tridecanoic acid methyl esters, gamma and beta sitosterol and Stigmasterol, 1-docosene and lastly 1-nonadecene hence these compounds are more likely to cause pitch. After analysis using UV analysis and acidolysis there was indication that there were lignin breakdown products present in the wood extracts, in minimal amounts. HPLC indicated no sugars present in the extracts. It is concluded that GC and GC-MS are the recommended analytical tools in characterising and quantifying wood extractives in E. grandis and E. nitens. All extractives in both species were quantified and identified using GC and GC-MS respectively. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2011.

An attempt to obtain chiral induction across the carbamate linkage (-NCOO-), using chiral amines and the benzyl carbamate, was embarked upon. Initial studies centred around the benzyl carbamate protected form of a,a-diphenylpyrrolidinemethanol. The inability to protect the alcohol in this compound led to further investigations into differently structured molecules, these being 2-(1-phenylcyc1opentyl)-4,4,6-trimethyltetrahydro-l,3-oxazine and N-biphenyl benzyl carbamate. Chiral induction was not achieved, but the investigations therein led to two new fields of study. A trans-carbamation type cyclisation reaction was found to occur in the a,a-diphenyl-(2pyrrolidine- N-benzyl carbamate)methanol compound yielding the bicyclic 2-oxazolidone, 3-oxa-l-aza-4,4-diphenylbicyclo[3.3.0]octan-2-one, with nitrogen at the bridgehead position. Sodium hydride was the base used to facilitate this reaction. Further studies into this reaction and this class of compounds were inconclusive. The second field of study was the initial investigation into novel N-monosubstituted carbamate rearrangement reactions to yield a substituted alcohol, of the benzyl alcohol type. The rearrangement occurs when the carbamate is treated with butyllithium at O°C and the reaction allowed to warm to room temperature. The rearrangement was shown to occur when the substituent on the nitrogen is aromatic in nature, this group being able to contain a hetero-atom and be substituted. A positive result was also obtained when the 0-carbamate moiety was the benzyl or cinnamyl group and to a much lesser degree the allyl group. The products obtained from the rearrangement of the benzyl carbamates were a-aryl- a-phenylmethanols (substituted benzyl alcohols / benzhydrols), with the analogous product, l-aryl-3-phenylprop-2-en-l-ol, being obtained from the cinnamyl alcohol. A benzylic substituted benzyl carbamate rearranged to give the tertiary alcohol. It was found that the rearrangement occurred to the position on the aryl substituent to which the nitrogen had been attached. From the results obtained no conclusive mechanistic details could be determined, but it was proposed that the reaction intermediate contained a five-membered cyclic structure. It is assumed that the rearrangement occurs with concomitant loss of cyanic acid (HNCO). / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1996.

The aim of this project was to synthesize xanthoxal, a natural product which is a possible abscisic acid precursor. The xanthoxal will serve as a vital link: in a study on the biosynthesis of abscisic acid in plants. This study does not form part of this thesis. The synthetic pathway begins with mesityl oxide and ethyl acetoacetate as starting materials, and the target molecule was obtained via a I3-step route. The first step involved a Robinson annulation, which afforded the ketal of a ClO-ester ketone (ethyl2,6, 6-trimethyI4-oxo2-cyclohexene-I-carboxylate) which has a cyclohexene structure. The double bond in the 2,3 position of the ClO-ester ketone was isomerised to the 1,2 position followed by the simultaneous protection of the ketone, in the form of a ketal. The ester function of the ClO-ester acetal underwent reduction to afford an allylic alcohol . on which an asymmetric Sharpless epoxidation was carried out using (-) diethyl tartrate affording (+)-(1R, 2R)-I,2-Epoxy-4, 4-ethylenedioxy-2,6, 6-trimethylcyclohexane-lmethanol. The alcohol was oxidised by a Swem oxidation to the aldehyde in order to carry out a chain elongation. The side chain was prepared from 3,3-dimethylacrylic acid, which was first esterified then brominated to 4-bromosenecioate. The bromine was then replaced with triethyl phosphite, producing the Cs-phosphonate. Chain elongation by Homer-Emmons reaction was carried out on the aldehyde with the phosphonate, which resulted in a mixture ofE and Z CIs-esters. Since the yield of tht desired Z isomer, was very low, the E isomer was used to synthesize trans-xanthoxal, since this can be converted to the desired xanthoxal by uv radiation. The acetal was then removed followed by a simultaneous reduction of the ketone and ester groups to their corresponding alcohols using DffiAH. This reaction was only partially successful because only the keto group was reduced. The ester was then reduced with LiAIHt to form the primary alcohol, which was then selectively oxidised to the target molecule, the aldehyde (trans-xanthoxal). The synthesis of xanthoxal described here highlights the difficulties encountered when introducing the requisite functional groups on the cyclohexene ring skeleton to afford trans-xanthoxal. The pitfalls encountered during the reaction sequence are discussed and solutions are presented. Although the planned synthetic sequence did not produce the correct stereoisomer, procedures are available to convert it to the desired isomer. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1999.

A comparative study of the activation of n-hexane over the 12-molybdophopshoric acid (H3PMo12O40 or HPA), its Fe3+ doped salt (Fe0.69H0.93PMo12O40 or Fe doped HPA) and the iron phosphate catalyst (P/Fe = 1.22) was carried out. It was found that the Fe doped HPA catalyst is thermally more stable and less acidic that the HPA catalyst. The HPA and the Fe doped HPA catalysts were more reactive that the iron phosphate catalyst. Both the HPA and Fe doped HPA catalytically produced 2,5- dimethyltetrahydrofuran and 2,5-hexadione (oxygenates), with the Fe doped HPA catalyst selectively producing more oxygenates than the HPA catalyst. This implied that the Fe3+ cation promoted the oxygen insertion reactions. The iron phosphate catalyst catalytically produced cis-2-hexene and 1- hexene but did not produce oxygenates, which means that the iron phosphate catalyst promotes oxidative dehydrogenation but does not promote oxygen insertion reactions. At 349 oC, the HPA catalyst played a role in initiating benzene formation. At isoconversion, the iron phosphate catalyst produced the highest yield of benzene (5.8 % at 8.1 % hexane conversion), which may have formed through both catalytic and non-catalytic reactions. The Fe doped HPA catalyst produced a lower benzene yield (1.4 % at 6 % hexane conversion) than the HPA catalyst (3.6 % at 8.3 % hexane conversion) at almost isoconversion and isothermal conditions. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2009.

A novel platinum(II) complex, [Pt{4-(o-tolyl)-6-(3˝-isoquinoyl)-2,2´-bipyridine}Cl]SbF6 (Pt4) was synthesized and characterised by means of infrared, elemental analysis, mass spectroscopy, and NMR spectroscopy. Substitution kinetics of chloride ligand from square planar platinum(II) complexes namely; [Pt(2,2´:6´,2˝-terpyridine)Cl]Cl·2H2O (Pt1), [Pt{2-(2´-pyridyl)-1,10-phenanthroline}Cl], (Pt2), [Pt{4´-(o-tolyl)-2,2´:6´,2˝-terpyridine}Cl]CF3SO3 (Pt3) and [Pt{4´-(o-tolyl)-6-(3˝-isoquinoyl)-2,2´-bipyridine}Cl]SbF6 (Pt4) were studied using a series of five-membered heterocyclic neutral nitrogen donor nucleophiles, viz. pyrazole (Pz), triazole (Tz), imidazole (Im), 1-methylimidazole (MIm) and 1,2-dimethylimidazole (DMIm) under pseudo first-order conditions in methanol. The kinetics of the substitution reactions were studied as a function of concentration of the nucleophiles at different temperatures using UV/Visible spectrophotometry and conventional stopped-flow techniques. The observed second-order rate constants, k2 followed a two term rate law kobs = k2[Nucleophile] + k-2 except for 1,2-dimethylimidazole with Pt1, Pt3, Pt4 and Pz and Tz with Pt1. The observed second-order rate constants along with the negative entropies of activation support an associative mode of substitution behaviour. The results obtained indicate that increasing the π-conjugation in the cis and cis/trans position influences the rate of substitution reactions. Increasing the π-conjugation in the cis position decreases the rate of the substitution reactions by decreasing the π-acceptor property of the terpy moiety. On the other hand, increasing the π-conjugation in the cis/trans position increases the rate of substitution reaction by enhancing the π-acceptor property within the ligand framework. This in turn increases the electronic communication, which consequentially decreases the frontier orbital energy gap between HOMO and LUMO and hence increases the reactivity of the metal centre. Thus the observed trend for the reactivity was Pt2 > Pt1 > Pt3 > Pt4. The observed kinetic trend was further supported by DFT-calculations obtained from the computational analysis carried out for the complexes. The substitution kinetics was influenced by the basicity of the incoming nucleophiles. Except for the sterically hindered nucleophile, DMIm, the pKa of the entering nucleophiles followed a Linear Free Energy Relationship (LFER) indicating an increase in the substitution reactions with increase in the basicity of the nucleophile. The general trend observed for the reactivity of the nucleophiles is MIm > Im > DMIm > Pz > Tz. In the reverse reactions the replacement of the azoles by the chloride was controlled by the strength of the Pt—N(azole) bond which is dependent on the strength of the extent of the π-back-bonding between the platinum centre and the azole. / Theses (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.

There is a constant need for robust and highly reactive hydroborating reagents which will be able to yield stable organoborane compounds upon their hydroboration with olefins. These stable organoborane compounds can be used as a starting material in a number of cross-coupling reactions. The objectives of this project were to synthesize heterocyclic borolanes (with mixed donor atoms) and to evaluate the stability and reactivity of such borolanes towards the hydroboration reaction. The second part of the objective was to evaluate the application of arylbenzo-1,3,2-diazaborolane compounds as potential arylating reagent in the copper(II)acetate catalyzed N-arylation of imidazole using the Chan-Lam coupling reaction. Three heterocyclic borolanes were successfully synthesized from the reaction of borane-dimethyl sulfide complex with the corresponding chelating group in yield ranging from 45-96 %. These borolane showed good stability towards atmospheric oxidation and disproportionation due to elevated temperatures. A density functional calculation conducted on these borolanes showed that there was an decrease in the gap energy in the order of benzo-1,3,2-dioxaborolane > benzo-1,3,2-oxothiaborolane > benzo-1,3,2-thiazaborolane > benzo-1,3,2-dithiaborolane > benzo-1,3,2-diazaborolane. The use of benzo-1,3,2-thiazaborolane as a hydroborating reagent showed that this compound was prone to disproportionation. The condensation reaction of boronic acid with 1,2-diaminophenyl, 1,2-dihydroxybenzene and o-aminophenyl mercaptan, resulted in the synthesis of eleven arylbenzo-1,3,2-boronate esters in yields between 66-99 %. The investigation on the use of arylbenzo-1,3,2-diazaboronate ester as N-arylating reagents in the Chan-Lam coupling showed that these compounds were unsuitable arylating reagents and that the boronic acid proved to be better arylating reagent. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2013.

In the present study the acetone extract of the heartwood of two trees, Virgilia oroboides and Chlorophora excelsa, were investigated. The heartwood of Virgilia oroboides afforded a variety of known flavonoids, as well as a new pterocarpene and a new α-hydroxydihydrochalcone, viz.; 3-hydroxy-8, 9-methylenedioxy-6a,11a-dihydropterocarpan (αS), 2' ,4'-trihydroxy-4-methoxydihydrochalcone. A series comprising substituted hydroxygeranylstilbenes, substituted benzenoid compounds and quercitin-type flavones were isolated from the acetone extract of the heartwood of Chlorophora excelsa. The new compounds isolated from this tree are: 3,5-dihydroxy-4-geranylbenzaldehyde; 3' ,4,5'-trihydroxy-4'-geranylstilbene; 2'-methoxy-3, 4',7-tri-O-methylquercitin. A combination of solvent extraction, Craig countercurrent, column (LH 20 and silica gel) and thin layer chromatography procedures were used to isolate and purify the compounds mentioned. Structures were elucidated by high resolution (300 MHz) ¹HNMR spectroscopy (including NOE and spin-spin decoupling experiments) and mass spectrometry. The proposed structural assignments of the following compounds were confirmed by synthesis: 3, 5-dihydroxy-4-geranylbenzaldehyde; 3' ,4 ,5'-trihydroxy-4' -geranylstilbene; 2 ,3' ,4 ,5'-tetrahydroxy-4' -geranylstilbene (chlorophorin). The modified Wittig reation was used to synthesize 3' ,4 ,5' trihydroxystilbene. U.V. irradiation experiments were performed on chlorophorin in an attempt to synthesize the cis-isomer and a phenanthrene-type compound. Biosynthetic pathways showing the structural relationships of the identified compounds in Virgilia oroboides and Chlorophora excelsa were proposed. An attempt to synthesize (+)-catechin lignoid involved the coupling of (+)-catechin to sinapyl alcohol, with the latter synthesized from 2 ,6-dimethoxyphenol via vinyl quinone methide. Further investigations on lignoid currently in progress. / Thesis (M.Sc.)-University of Durban-Westville, 1989.

The carbamate functionality has always been associated with a major class of biocides because of its ability to function as an inhibitor of the enzyme acetylcholinetransferase. However, carbamates are not limited to pesticidal applications, they have also shown potential as intermediates in organic synthesis. Research has shown that amongst its other properties, the carbamate group has the ability to migrate, function as a leaving group and participate in rearrangement reactions. As part of ongoing research at this department on the synthetic utility of the carbamate group, this project has been primarily concerned with the chemistry of carbamates in conjunction with thiophene, an aromatic heterocycle. The thiophenes also represent an important class of organic compounds. They are found in natural products, biologically and pharmacologically active systems (both naturally occurring and synthetic), synthetic precursors and more recently, organic conductors and electro-optical devices. In exploring the chemistry of thiophene carbamates, the unique nature of the thiophene ring has been shown to affect the synthesis and reactions of these compounds; the often peculiar character of thiophene imparts properties which make these carbamates remarkable and distinct from carbamates of other aromatic and conjugated systems such as benzene and conjugated polyenes. With a wide range of potential applications, the purpose of this project has been to study the synthesis and reactions of thiophene carbamates, in particular, the reaction of deprotonated thenyl carbamates with electrophiles, using the electrophile as a means of studying the charge delocalisation in such systems. A series of thenyl carbamates has been synthesised from thenyl alcohols and their reactions with electrophiles have been studied. The electrophilic substitution reactions illustrate the possibilities for the functionalisation of these compounds, particularly remote functionalisation via anionic charge migration; the charge has been found to migrate across five carbon atoms, a phenomenon not observed in this department's studies of other carbamate systems. The substitution products which form in these reactions depend on the nature of both the carbamate and the electrophile. In addition, three rearrangements (carbamate to amine, substituted carbamate to alkene, and substituted carbamate to a-hydroxyamide) have been observed which may find application in organic synthesis. The potential uses for these carbamates range from biologically active applications as carbamates or as derivatives (amines or alkenes via rearrangement or alcohols via deprotection); many contain a chiral centre and thus may be used in enantioselective or diastereoselective processes in the synthesis of other products, as well as the industrial applications in the fields of non-linear optics and conducting polymers. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1996.

This study reports a series of promising and structurally diverse potential HIV-1 protease inhibitors. Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immune Deficiency Syndrome (AIDS). HIV infection disrupts the immune system and makes the body susceptible to opportunistic infections. If untreated, AIDS is generally fatal. Today, AIDS has become a long lasting pandemic. According to the World Health Organization (WHO) and Joint United Nations Program (UNAIDS-2009) report, it is estimated that 33.3 million men, women and children worldwide are infected with HIV. This situation is steadily deteriorating in some parts of the world compared to the previous years. One of the major drawbacks associated with the currently FDA-approved anti-HIV drugs are severe side effects, toxicities, high dosage and high treatment cost. Thus, an urgent need for new drugs to combat HIV is apparent. In the first part of the study, research efforts were focused to synthesize potent pentacycloundecane (PCU) derived peptide and peptoids as protease inhibitors. It is proposed that these inhibitors bind to wild type C-South African HIV protease (C-SA) catalytic site via a non-cleavable or non-hydrolysable cyclic ether bond for the first polycyclic cage compound and via a dihydroxylethelene type functional group for the second cage compound. The desired compounds were synthesized by coupling of the peptides and peptoids to the PCU derived cage. Second part of the study involves, biological evaluation against wild type C-SA enzyme and characterization of the synthesized compounds by Nuclear Magnetic Resonances (NMR). All the synthesized novel compounds were evaluated against wild type C-SA enzyme for their ability to inhibit 50% of the enzyme’s activity (IC50). Some of the compounds reported herein showed promising activity by inhibiting the enzyme activity at concentrations of less than 0.6 nM. 2D NMR investigations employing a new Efficient Adiabatic Symmetrized Rotating Overhauser Effect Spectroscopy (ROESY / NOESY) technique enabled the attainment of vital information about the 3D structure of these small linear peptides and peptoids in solution. The activity could be related to conformations induced by the PCU moiety on the coupled peptide side chain. Further quantum mechanics/molecular mechanics/molecular dynamics (QM/MM/MD) simulations were carried out to confirm the observed NMR experimental results. Docking studies were performed for the synthesized compounds. Binding energies obtained from the docking calculations were then used to further validate the experimental IC50 results. These experimental and theoretical methods provided valuable insight into the interaction mode of these cage peptide and peptoids inhibitors with the enzyme. / Thesis (Ph.D.)-Unversity of KwaZulu-Natal, Westville, 2012.