3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Lipase-catalysed hydrolysis of morita-baylis-hillman adducts(2019) Mguni, Lindelo MthabisiBiocatalysis is the use of biological systems, such as enzymes, to perform chemical transformations on organic compounds. These enzymes catalyse reactions as whole cell systems or in isolated forms and have been found to exhibit high regio- and stereoselectivity towards chiral compounds. Lipases have been extensively used to catalyse kinetic resolutions of chiral compounds such as the Morita-Baylis-Hillman (MBH) adducts. The MBH adducts and their esters are important intermediates in organic synthesis and have been found to be valuable in the production of biologically active compounds. In this study, we expressed and partially purified the Pseudomonas fluorescens P26504 lipase in an active and soluble form to catalyse the kinetic resolution on MBH acetates to obtain enantiopure MBH adducts. The Pseudomonas fluorescens P26504 lipase was overexpressed in BL21 (DE3) pLysS cells at 25 °C for 16 hours, with 1mM IPTG concentration. Enzymatic assays were conducted after partial purification using p-nitrophenyl esters. The recombinant enzyme was highly active towards short chain esters and showed moderate activity towards medium chained esters. The Morita-Baylis-Hillman reaction was conducted, giving rise to racemic MBH adducts derived from benzaldehyde and hydro-cinnamaldehyde. The second step of the reaction was acetylation, producing chiral MBH acetates. A lipase-catalysed kinetic resolution was set-up, using the partially purified recombinant P. fluorescens P26504 lipase and the MBH acetates. TLC plate analysis showed that the recombinant lipase was able to hydrolyse both MBH acetates. However, further studies can be done to determine the enantioselectivity of the recombinant P. fluorescens P26504 lipase using chiral HPLC, which is more definitive.Item An investigation of the enzymatic kinetic resolution of Morita-Baylis-Hillman adducts and their further functionalisation(2019) Juma, Wanyama PeterThe Morita-Baylis-Hillman reaction (MBHR) is a carbon-carbon bond forming reaction that affords multifunctional Morita-Baylis-Hillman adducts (MBHA) with various synthetic applications. Unfortunately, many of the synthetic applications of these adducts cannot be realised because these adducts are formed in racemic form. This thesis has investigated functionalisation of enantiopure MBHA obtained using biocatalytic methods. The first part of the thesis describes the use of enantiopure aldehydes N-Boc-L-phenylalaninal and N-Boc-D-phenylalaninal to synthesize several Morita-Baylis-Hillman adducts in order to obtain diastereomers that would be separable by chromatographic methods. Unfortunately, this approach proved unsuccessful due to racemization of the aldehydes or MBHA under the reaction conditions applied. The second approach described is the resolution of racemic MBH acetates and esters using different enzymes. This exercise led to the identification of several lipases that were able to resolve racemic MBH acetates with excellent enantiomeric excess (ee) values and enantiomeric ratios (E). Racemic MBH adducts derived from the reaction of acrylonitrile with benzaldehyde, cinnamaldehyde and hydrocinnamaldehyde were successfully resolved. In each case the (+)-alcohol products were isolated in 94 - 97% ee after lipase-mediated enzymatic kinetic resolution of the corresponding acetates. Mosher’s ester derivatisation protocol was used to determine the absolute configuration of the resolved adducts, which was found to be (S). A lipase from Pseudomonas fluorescens, and Candida antarctica type B were found to be the best-performing enzymes. The last part of the thesis investigated the use of nitrogen nucleophiles for Michael addition to MBH adducts. The process confirmed that the use of nitrogen nucleophiles on TBS protected MBH adducts afforded nucleophilic addition products of high diastereoselectivity. The use of one of the enantiopure isolated MBH adducts in a diastereoselective Michael addition reaction with benzylamine led to a significantly enantio-enriched final product.Item Impact of microwave irradiation on the properties of the manganese oxide based electrode materials for lithium-ion and sodium-ion batteries(2018) Nkosi, Funeka PhumzileThis work involved the study of manganese oxide based materials as cathode materials in lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). A lithium manganese richtransition metal oxide, Li1.2Mn0.52Co0.13Ni0.13Al0.02O2 (LMNCA) cathode material was successfully prepared using the combustion method. Urea and ethylene glycol (EG) were used as fuels during the combustion synthesis and their effect on the physical and electrochemical properties of the samples were evaluated. This study revealed that the combustion synthesis of electrode materials depends greatly on the type of fuel to produce materials with enhanced electrochemical properties. LMNCA prepared by urea (LMNCA-urea) delivered the higher specific capacity of 295 mAhg with a capacity retention of 84 percent after 50 cycles, while the LMNCA prepared by EG (LMNCA-EG) gave a capacity of 240 mAhg and a capacity retention of 78 percent after 50 cycles. Even though LMNCA-urea has enhanced cycle performance, it has higher voltage fade and decomposition of electrolyte occurs upon cycling as compared to LMNCA-EG. The effect of microwave irradiation on the combustion synthesis of LMNCA using either the urea or EG was also studied. The microwave irradiation improved the capacity and the rate capability of LMNCA-EG by decreasing the particle size and tuning the oxidation state of the manganese ion content. The capacity retention after 50 cycles at 0.1 C is 88 percent and 82 percent for LMNCA-EG and LMNCA-urea, respectively. The XRD analysis revealed pure, crystalline LMNCA powders with good hexagonal ordering. The SEM images showed that LMNCA powders exhibited plate-like particles with smooth surfaces, an unusual morphology for LMNCA materials. The LMNCA material exhibited excellent cycle performance and good rate capability. The capacity retention was 95 percent and 96 percent after the 50th and 100th cycles, respectively. The preparation of P2-type Na0.67Mg0.28Mn0.72O2 (NaMgMnO) cathode materials for sodium-ion batteries using a urea combustion method is also reported for the first time. The effect of microwave irradiation and fluorination was investigated with the aim to improve the capacity retention and the rate capability of NaMgMnO cathode material. The powder XRD analyses showed that pure single phase P2-type powders were successfully prepared. SEM analyses revealed an impact of microwave irradiation and fluorination on the morphology of the materials. The galvanostatic charge-discharge and the electrochemical impedance spectroscopy studies showed that both microwave irradiation and fluorination improved the capacity, coulombic efficiency, cycle performance and impedance of NaMgMnO cathode materials.Item Enaminone-based approaches to the synthesis of alkaloids possessing the pyrrolo[1,2-a]azepine core(2018) Mthembu, Siyanda ThabaniThis thesis illustrate strides taken toward the construction of the pyrrolo[1,2-a]azepine 4 nucleus via enaminone chemistry developed in this University for creating pyrrolizidine 1, indolizidine 2 and quinolizidine 3 alkaloids. The pyrrolo[1,2-a]azepine 4 core is a fused pyrrolidine and azepine system found in lehmizidine, Stemona, Cephalotaxus alkaloids and other alkaloids. A concise background is given on the nature of enaminones, how they are accessed with strong emphasis on the Eschenmoser sulphide contraction reaction and their versatile reactivity, followed by literature review of this University background on synthesis of alkaloids containing 1, 2 and 3 nuclei. The aims and strategies presented are preceded by literature review of lehmizidine, Stemona, Cephalotaxus alkaloids and some reported synthesis. A range of attempts and successes are reported in chapter 2 for making four-carbon chain length enaminones (via N-alkylation, condensation, thionation, Eschenmoser sulphide contraction and tandem acylation/Michael addition reactions) crucial in creating azepane onto pyrrolidine in an acylation or alkylation ring closing steps yielding lehmizidine like compounds (E)-ethyl 8-oxo- 2,3,5,6,7,8-hexahydro-1H-pyrrolo[1,2-a]azepine-9-carboxylate 144 and (E)-ethyl 2,3,5,6,7,8- hexahydro-1H-pyrrolo[1,2-a]azepine-9-carboxylate 147. Vice versa, the synthesis of two carbon chain length N-alkyl vinylogous amides is demonstrated leading to the formation of pyrroles, ethyl 2-phenyl-6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-3-carboxylate 222, ethyl 2-(4-nitrophenyl)- 6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-3-carboxylate 223 and ethyl 2-(4-methoxyphenyl)- 6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-3-carboxylate 224 in Knoevenagel condensation reactions similar to those described by Garreth Morgans and Stefania Scalzullo in their PhD theses. The synthesis of 1-benzoyl-6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-2,3-dione 233 and 1-(4-methoxybenzoyl)-6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepine-2,3-dione 235 in a double acylation reaction between NH vinylogous amides and oxalyl chloride is also demonstrated. In chapter 3, the synthesis of vinylogous urethanes for making the Cephalotaxus core via Nalkylation, condensation, thionation, Eschenmoser sulphide contraction and tandem acylation/Michael addition reactions are described. A variety of attempts of the arylation reaction on vinylogous urethanes are demonstrated leading to a comparison study to ascertain carbon chain length dependency of the step. The synthesis of pyrido[1,2-a]azonine nucleus of Sessilifoliamide alkaloids, which are a subset of the Stemona alkaloids demonstrated in chapter 4 is in line with our fascination with bigger ringed alkaloids. The synthetic route is presented leading the formation of compounds 1-benzoyl-3- methyl-2,3,7,8,9,10,11,12-octahydropyrido[1,2-a]azonin-4(6H)-one 337, 3-methyl-1-(4- nitrobenzoyl)-2,3,7,8,9,10,11,12-octahydropyrido[1,2-a]azonin-4(6H)-one 338 and 1-(4- methoxybenzoyl)-3-methyl-2,3,7,8,9,10,11,12-octahydropyrido[1,2-a]azonin-4(6H)-one 339.Item Development of novel methodology for the synthesis of the angucycline tetrangulol, benzo[c]phenathridines and benzonaphthopyranones(2017) Ngwira, Kennedy John VijuvijuIn this PhD thesis, we report for the first time, new methodology for the synthesis of angucycline antibiotic natural products. In particular, for the synthesis of 1,8-dihydroxy-3methyltetraphene-7,12-dione, commonly known as tetrangulol. We also report on the synthesis of 1,10,12-trimethoxy-8-methylbenzo[c]phenanthridine in our quest to synthesise phenanthroviridone from an intermediate product in the synthesis of tetrangulol. The Suzuki-Miyaura coupling reaction between 1,4,5-(trimethoxynaphthalen-2-yl)boronic acid and 2-iodo-3-methoxy-5-methylbenzaldehyde afforded intermediate, 3-methoxy-5methyl-2-(1,4,5-trimethoxynaphthalen-2-yl)benzaldehyde. Conversion of this benzaldehyde into the alkyne, 2-(2-ethynyl-6-methoxy-4-methylphenyl)-1,4,5-trimethoxynaphthalene was accomplished utilizing the Corey-Fuchs reaction. Exposure of the derived acetylene to a catalytic platinum(II)-mediated ring closure yielded the required tetracyclic aromatic product, 1,7,8,12-tetramethoxy-3-methyltetraphene which was converted into tetrangulol. Exposure of the related 3-methoxy-5-methyl-2-(1,4,5-trimethoxynaphthalen-2-yl)benzaldehyde O-phenyl oxime to microwave irradiation in an ionic liquid yielded 1,10,12-trimethoxy-8methylbenzo[c]phenanthridine, instead of the desired natural product phenanthroviridone. We also report on the unexpected synthesis of the benzonaphthopyranone core found in other classes of angucycline antibiotics from oxygen analogs of 2-naphthylbenzyl alcohols when exposed to N-bromosuccinimide. Treatment of (2-(1,4-dimethoxynaphthalen-2yl)phenyl)methanol and related analogues with N-bromosuccinimide under an oxygen atmosphere afforded 12-methoxy-6H-dibenzo[c,h]chromen-6-one, 2-Methoxy-6Hbenzo[c]chromen-6-one and of 6H-benzo[c]chromen-6-one. An investigation into possible mechanisms for this transformation was also conducted.Item The synthesis of 3,5-disubstituted indolizidines(1996) Cheesman, Penelope, SueAspects of the literature of the ant venom alkaloid monomorine I and its stereoisomers were reviewed. Racemic 5-butyl-2-pyrrolidinone was synthesised in two steps from methyl acrylate and 1-nitropentane, A thionation step yielded 5-butylpyrrolidine-2-thione. The Michael addition reaction between 5-butylpyrrolidine-2-thione and ethyl crotonate proceeded with difficulty to form a separable mixture of diastereomers of 5-butyl-l-(2-ethoxycarbonyl-l-methylethyl) pyrrolidine-2-thione. [Abbreviated Abstract. Open document to view full version]