Pyrolysis gasoline (PyGas) is a by-product of high temperature naphtha cracking during ethylene and propylene production. It is a high octane number mixture which contains aromatics, olefins and paraffins ranging from C5s to C12s. PyGas has high potential for use as a gasoline blending mixture and/or as a source of aromatics. Currently, PyGas is generally used as a gasoline blending mixture due to its high octane number, but global production of PyGas is very high and further increases are anticipated in the future due to higher demands for ethylene and propylene. However, current strict fuel regulations for aromatic content make PyGas utilisation as a blending mixture more difficult, therefore a useful avenue for PyGas consumption is desired. Catalytic hydrogenation of PyGas is an important industrial and academic research area for the stabilisation, upgrading and utilisation of PyGas. Limited work has been performed on the hydrogenation of PyGas and an incomplete picture of the process has been obtained. The composition of PyGas is very complex and therefore most of the studies have been carried out with single compounds or a mixture of a few model compounds for simplicity and generality. However, the single model compound cannot be representive of the entire PyGas hydrogenation process. Furthermore, the behaviour of these compounds is generally different in mixtures than as individual compounds. Hence, the hydrogenation of a PyGas, which contained styrene, toluene, 1-octene, cyclopentene, heptane, decane and 1,3-pentadiene/1-pentene, was investigated over alumina supported nickel and palladium catalysts. This is a comprehensive model for the broader groups of hydrocarbons present in PyGas. The aim of the work was to investigate the effect of reaction parameters such as reaction temperature, total reaction pressure, hydrogen partial pressure and WHSV of PyGas on the hydrogenation of PyGas. Different strategies were proposed for PyGas consumption to obtain; (i) a high octane number gasoline blend, (ii) an aromatic source mixture and (iii) hydrogenation of surplus aromatics present in PyGas. These desired products were achieved during PyGas hydrogenation over both the nickel and palladium catalysts by using different reaction conditions. However, the palladium catalyst was found to be preferable for the selective hydrogenation of reactive species such as styrene, diolefins and for the isomerisation of olefins, without the hydrogenation of aromatics during PyGas hydrogenation at mild reaction temperatures. However, surplus aromatics hydrogenation can be achieved over the palladium catalyst with an increase in reaction temperature. Conversely, a greater amount of aromatics saturation was observed during PyGas hydrogenation over the nickel catalyst. Therefore the nickel catalyst was found to be preferable when aromatic ring saturation is desired during PyGas hydrogenation. The selective hydrogenation of PyGas without aromatics saturation was achieved over a nickel catalyst when using a low hydrogen partial pressure. The kinetics of PyGas hydrogenation were also investigated for a better understanding of the process. The apparent orders for hydrogenation /isomerisation of the PyGas components were investigated by using an empirical rate equation. During PyGas hydrogenation, first order (1.1 to 1.6) kinetics were observed for the hydrogenation of olefins to their respective paraffins over both the nickel and palladium catalysts with an increase in hydrogen partial pressure, which became zero or negative order kinetics when sufficient amounts of hydrogen were available on the surface of the catalyst. Negative order kinetics were observed for olefin isomerisation to internal olefin with an increase in hydrogen partial pressure. Meanwhile the hydrogenation of styrene to ethylbenzene followed zero order kinetics with respect to hydrogen over both catalysts due to the strong adsorption of styrene onto the catalyst. Third order kinetics were observed for aromatics hydrogenation over both catalysts. On the other hand, the hydrogenation of olefins to paraffins followed zero to negative order (0 to -0.7) kinetics, whilst positive order (1.6 to 3.6) kinetics were observed for isomerisation of olefins to internal olefins with respect to PyGas. Moreover, positive order (0.7 to 1.0) kinetics were observed for styrene hydrogenation to ethylbenzene with respect to PyGas. The hydrogenation of aromatics followed negative orders kinetics with respect to PyGas over both catalysts due to competitive hydrogenation of the olefinic and aromatic components. Coke deposition is believed to be the main reason for catalyst deactivation during the PyGas hydrogenation reaction. The amount and nature of the coke deposited was investigated by in-situ temperature programmed oxidation (TPO). The increase in reaction temperature not only increased the amount of coke deposition but also produced more condensed hydrogen deficient type coke. Conversely, the carbon laydown decreased with an increase in hydrogen partial pressure. Larger amounts of coke deposition took place over the nickel catalyst when compared to the coke deposited over the palladium catalyst under identical reaction conditions. Moreover, a soft type coke (with lower C/H ratio) was deposited over the palladium catalyst, while a comparatively hard type coke (with higher C/H ratio) was deposited over the nickel catalyst. Both the nickel and palladium catalysts used during PyGas hydrogenation were effectively regenerated by in-situ TPO with no significant loss to their catalytic properties.

The unfavourable use of metal-based catalysts in organic synthesis can be overcome by using small organic molecules; organocatalysts. Herein we report the development and synthesis of a novel range of organocatalysts derived from amino acids incorporating imidazole, thiourea and phosphoramide moieties to confer the capability to act as bifunctional organocatalysts. Our organocatalyst, a phosphoramide derived from valine, showed initial success in the catalytic allylation of aldimine with allyltrichlorosilane, producing 40% ee. Oxazoline catalysts derived from 2-pyridines have been shown to be effective activators of trichlorosilane for the reduction of ketones and ketimines. The reaction however suffered from chloride promoted ring opening of the catalyst. By replacing the oxygen of the oxazoline moiety with sulphur we were able to successfully avoid this problem. Further expansion of the substrate scope was achieved, heterocyclic imines were reduced in good enantioselectivity, up to 89% ee.

The noradrenaline reuptake transporter is located on the pre-synaptic membrane of noradrenic neurons. Its main function is to terminate the action of the neurotransmitter noradrenaline by reuptake back into the nerve terminal. Changes in the function and density of the noradrenaline reuptake transporter have been implicated in neurological disorders such as clinical depression and Alzheimer’s disease. In vivo imaging of the noradrenaline transporter using single photon emission computed tomography has been hampered by the lack of a suitable imaging agent. The information from imaging studies could lead to a better understanding of transporter function and the development of more efficient and faster acting drugs to treat the diseases associated it. For the first time, all four stereoisomers of an iodinated analogue of reboxetine were stereoselectively synthesised and biologically evaluated in an effort to understand the relationship between stereochemistry and potency. All four compounds were found to have nanomolar affinity for the noradrenaline transporter. Of most interest was the (2R,3S)-stereoisomer, which was identified as being as potent as the more studied (2S,3S)-stereoisomer. Therefore, a new series of iodoanalogues based on the (2R,3S)-stereochemical scaffold were synthesised and tested for their affinity with the noradrenaline transporter. This study revealed the derivative with ortho substitution on the phenoxy ring to be a potential lead for the development of a novel imaging agent for the noradrenaline transporter.

The tetrahydrofuran backbone is one of the most common heterocyclic units found in natural products. Among them structurally complex substituted tetrahydrofuran rings which present a 2,5-trans stereochemistry have been of particular interest to many groups as polyether antibiotics and highly biologically active compounds, such as the potent anti cancer Amphidinolide, possess this kind of backbone. Different methodologies to synthesise this kind of structure have been developped starting in the late 70’s. The first efficient methodology was published by Fukuyama in Tetrahedron Letters in 1978. It involves the stereospecific epoxidation of bishomoallylic alcohol using VO(acac)2. Treatment of the epoxide with acetic acid led to the desired 2,5-trans-tetrahydrofuran in up to 20:1 ratio. In 1990, Inoki developed an efficient method for the synthesis of trans-tetrahydrofurans. Using this methodology, 5-hydroxy-1-alkenes can be converted to the desired cyclisation product via oxidative cyclisation with molecular oxygen using cobalt complex as a catalyst. The 5-hydroxy-1-alkene react with the Co complex and the oxygen. The radical complex thus formed could be converted to the cyclised intermediate. The cyclisation occurs in reasonable yields (up to 79 %) and exellent trans selectivity (99 %). More recently Panek published a methodology involving the chelation controlled formation of trans tetrahydrofuran. A Lewis acid such as SnCl4 is able to form chelate with a α-benzyloxy group of an aldehyde. This activated intermediate can then undergo the electrophilic substitution. This method led to the trans cyclisation product in up to 40:1 ratio. In order to increase the level of diastereocontrol our group have investigated a methodology based on an intramolecular tandem carbenoid insertion and ylide rearrangement reaction of a diazoketone. This diazoketone undergoes a nucleophilic attack onto an empty d orbital of the transition metal. The transition metal back donates the electrons of one of its d orbital to the carbon to form the metal carbenoid with elimination of nitrogen. Attack of one of the lone pair of the oxygen onto the carbon bonded to the 3 transition metal led to the formation of the oxonium ylide which undergoes [2,3]-sigmatropic rearrangement. Previous studies made within the group have proved Cu(acac)2 to be the best catalyst for the synthesis of the trans-2,5-dialkyl tetrahydrofuran-3-ones. The stereochemistry observed could be explained by the stereochemistry of the substituent R1. The transition state shows clearly that the trans- rearrangement product is favoured. We have decided to apply this methodology to the synthesis of the (6S, 7S, 9S, 10S)-6,9-epoxynonadec-18-ene-7,10-diol. and the functionalised A-ring fragment of gambieric acid.

The main focus of this project has been the investigations into the effect that fluorine substitution has on structures of molecular complexes containing DNA base molecules. Previous work done on these molecules has been targeted at producing anti-cancer or antiviral treatments, which reflects an important ultimate aim of investigations in this area. Success in this structural project would make a contribution towards this aim, by helping the understanding of the effects of fluorination on some of the interactions that control DNA self-assembly, notably base-pairing and stacking interactions, together with additional interactions involving fluorine. The specific aim of this project was to grow crystals of molecular complexes of cytosine and 5-fluorocytosine with co-molecules and use the structural descriptions to assess the difference between the structures and the influence the presence of the fluorine atom has on the structure when compared to the nonfluorinated equivalent. Single crystal X-ray diffraction has been the main method of analysis, backed up by related techniques. Many crystallisations have been set up with cytosine and 5-fluorocytosine with a wide range of targeted co-molecules. 5-fluorouracil and uracil have also been used in related co-crystallisations with the aim of producing related complexes of these materials with the same co-molecules as used with cytosine and 5-fluorocytosine. In both families of complexes it was hoped that the fluorine would have an effect on the base-pairing motifs adopted in the structures, with the control being the non-fluorinated structure. The program dSNAP has been used to give a comparison of the structures produced in this work with those already reported in the CSD. This program has given an indication of the classification of the standard primary bonding motifs and to analyse the other features commonly seen in base pairs such as buckling and propeller twisting. The comprehensive series of complexes produced have provided the opportunity to examine significant structural trends, notable in the adoption of various base-pair motifs based on the Watson-Crick, Hoogsten and derived base-pairing patterns. The degree of proton transfer to the ring nitrogen of the cytosine could be rationalised in terms of the DpKa values, and the proton transfer has a substantial effect on the base-pair motifs able to be adopted. The classification of the complex structures in terms of hetero (pseudo)-basepairing has also been found to be of value. Extensive base-stacking and weaker interactions involving fluorine are also present; these have been analysed and found to have significant effects on the structures adopted, and hence may have future implications for the assembly of fluorinated DNA.

A one-pot, two step tandem process involving an Overman rearrangement and a ring closing metathesis reaction has been utilised for the efficient synthesis of various cyclic allylic trichloroacetamides from simple allylic alcohols. Various methods were then investigated for the allylic oxidation of a carbocyclic amide using TBHP along with different transition metals such as Pd, Se, Mn and Cr. This was required for the synthesis of the important building blocks for the construction of structurally diverse antiviral and anticancer carbocyclic nucleosides and natural products. The oxidation of (1S)-N-(cyclohexenyl)trichloroacetamide was then studied leading to the preparation of two diol analogues in excellent stereoselectivity. The cyclohexene derivative was also stereoselectively functionalised using Upjohn dihydroxylation conditions or by a directed epoxidation/hydrolysis sequence of reactions to generate two aminocyclitols, the enantiomer of dihydroconduramine C-1 and dihydroconduramine E-1 in excellent stereoselectivity. In addition to this, a one-pot tandem process involving a substrate-directed Overman rearrangement and ring closing metathesis reaction was developed for the stereoselective synthesis of a functionalised carbocyclic allylic trichloroacetamide. The functionalised carbocyclic amide was employed in the successful synthesis of a syn-(4aS,10bS)- phenanthridone framework using a Pd-catalysed cross-coupling reaction. Stereoselective epoxidation and dihydroxylation of the syn-(4aS,10bS)-phenanthridone was then investigated leading to the preparation of new analogues of 7-deoxypancratistatin. Attempts were also made to use the functionalised carbocyclic amide in the total synthesis of the Amaryllidaceae alkaloid (+)-γ-lycorane. Further studies were then investigated to expand the scope of the one-pot tandem process to include heterocyclic derived substrates. This led to a seven-membered carbocyclic amide, which has been modified to create a diastereomeric core of balanol.

Pectin methyl esterase (PME) enzymes are produced by bacteria, fungi and higher plants, and hydrolyse methyl ester groups present on the backbone of pectic polysaccharides found in the primary cell wall of plants. Pectic polysaccharides are required for intercellular adhesion in dicotyledonous plants. To fulfil this function, they need to be cross-linked, covalently or non-covalently. The texture of plant-based foods is affected by the location and extent of these linkages, ultimately determined by chemical and subsequent structural modifcations undergone by the methyl ester groups on the pectic polysaccharide backbone during growth, ripening, storage, cooking and processing. These processes result in spatial variations in cell separation and adhesion betwen the walls of adjacent cells. These modifications are due to the action of PME enzymes. It has been suggested that covalent intercellular linkages are formed by glycosidic bonds between xyloglucan and acidic pectins. However, the presence of non-methyl esters has been confirmed and these linkages are candidates for the role of intercellular adhesion. The correlation between the quantity of these non-methyl ester groups and the deterioration of potato tuber texture during the period of storage following harvest was explored in two potato cultivars using titrimetric techniques and atomic absorption spectrometry. Pectic methyl ester groups in plant material are a major reservoir of methanol in the biosphere. PME enzymes are responsible for the cleavage of the ester bond between theses methyl groups and the pectic polysaccharide backbone, resulting in the release of methanol and acidic pectin. Methanol from both anthropogenic and biogenic sources is an important precursor of the gaseous pollutant, tropospheric ozone. Thus the accurate quantification of methanol emitted to the troposhere from both growing and decaying plant material is essential as the global balance of gases in the Earth's atmosphere is continuously skewed as a result of anthropogenic activities. Particular principles and techniques used in the quantification of methyl ester groups in potato tubers were developed and utilised in order to quantify the amount of methanol contained in the leaves from tree species native to Great Britain, in the form of pectic methyl esters, that could potentially be emitted to the troposphere as a consequence of the senescence of these leaves. The potential impact on the quantity of methanol in the troposphere of the growth of certain crop species grown commercially in the UK was investigated. A modified bell jar headspace capture and purge emthod and thermal desorption technique, in conjunction with gas chromatographic (GC) quantification, were developed and used to quantify methanol emitted from the developing tissues of plant species with significant agronomical importance, both in the UK and globally. Results obtained from the determination of pectic methyl esters contained in mature leaves of tree species, native to Great Britain and growing sites in Scotland, were extrapolated using available leaf litterfall and leaf area index (LAI) data to account for total area of trees of the same species growing across Great Britain and the globe. The results obtained following the quantification of methanol emitted from growing plant species of agricultural significance were extrapolated to ultimately estimate the quantity of methanol being emitted from these plant species on a global scale annually.

The host-guest chemistry of two sets of isopolyoxometalate clusters is investigated. In particular the binding modes of cationic alkali and alkali earth metals through coordinative interactions with the cluster anions {Mo36} and {W36} were compared and contrasted. It was shown that the ionic radii of the cations are crucial in the isolation of discrete molecules or infinite 3D frameworks. Crystal engineering allowed the introduction of organic amine guest molecules by the formation of a set of intermolecular interactions between the cluster anions and the amine cations. In addition it was shown that by engaging the ammonium guest molecules in additional supramolecular interactions, the framework assembly in the solid state could be directed. Further investigations focused on the assembly of supramolecular polyoxometalate-based framework materials where organic ammonium cations were used as hydrogen-bond donors. The structural effects of three amines were compared and contrasted and it was established that the use of rigid planar molecules resulted in the formation of 2D networks whereas the use of flexible amines gave supramolecular 1D chains. Based on these results the synthesis of a functional framework was achieved; a three-component approach allowed the formation of a chiral, porous framework which shows structural stability and reversible solvent sorption properties. In a different approach, the cross-linking of polyoxometalates using transition metal linkers in organic solvents was studied. It was shown that silver(I) cations are highly versatile linking units and allow the linking of {V10} cluster anions into 1D zigzag chains and 2D planar networks. The silver units assemble into supramolecular, trinuclear complexes which are supported by bridging organic ligands. Careful choice of the reaction conditions allowed the formation of a 3D framework based on {W12} units. The tungstate clusters are cross-linked by dinuclear {Ag2} linkers which are held together by argentophilic silver-silver interactions and result in the formation of a porous framework. The material features reversible sorption capabilities and can be used to sequester small molecules as well as transition metal cations from organic solvents.

Flavan-3-ols such as (—)-epicatechin and (+)-catechin are found in significant concentrations in red wine, green and black teas and cocoa. The radiolabelling of flavan-3-ols for feeding studies would require a short high-yielding route from the point of introduction of the label. (E)-1,3-Diarylpropenes had been key intermediates in previous syntheses of flavan-3-ols and so the modified Julia alkenation reaction between a labelled aryl aldehyde and a 2-(2'-arylethylsulfonyl)benzothiazole was proposed as the key step in the preparation of radiolabelled (E)-1,3-diarylpropene. A low molecular weight poly(ethyleneglycol)-monomethyl ether (MPEG, average MW 550) support would be used to improve the efficiency of isolating radiolabelled product after each reaction. The light MPEG support was attached to the starting aryl bromide by protecting the phenolic hydroxyl group with a new light MPEG α,α’-dioxyxylyl protecting group, introduced by reaction with light MPEG-supported benzylic bromide, to give supported aryl bromide. The aryl bromide was reacted with copper (I) cyanide to give MPEG-supported nitrile. In theory, 14C-labelled cyanide could be used in this step. Reduction and hydrolysis gave the aldehyde. Throughout the sequence MPEG solid-phase extraction (M-SPE) was used to assist purification. Several approaches to the synthesis of 2-(2'-arylethylsufonyl)benzothiazole were then investigated using a variety of model 2-arylethyl sulfones. The novel addition of phenylcopper to phenyl vinyl sulfone gave 2-phenethyl phenyl sulfone in good yield, but the reaction was less effective for sterically hindered arylcoppers and unsuccessful for the preparation of 2-(2'-arylethylsufonyl)benzothiazoles. Alkylcopper reagents were also suitable substrates for this novel coupling. Heck reaction between aryl iodide and phenyl vinyl sulfone, and reduction of the resulting alkene gave 2-arylethyl phenyl sulfone but the Heck reaction failed with benzothiazolyl analogues. Lithiated 2-(methylthio)benzothiazole reacted with aryl aldehydes to give β-hydroxy sulfides, but reduction to 2-arylethyl derivatives failed, even after oxidation of the sulfide to the sulfone or elimination to give a vinyl sulfide or sulfone. The same problem was encountered when lithiated 2-(trimethylsilylmethylthio)benzothiazole was use to make vinyl sulfides directly. However, alkylation of lithiated 2-(methylthio)benzothiazole with benzyl bromide gave 2-(2'-phenylethylsufonyl)benzothiazole in good yield. Unfortunately, the reaction could not be used to prepare phloroglucinol-derived benzothiazole. Finally, the benzothiazoles underwent modified-Julia alkenation reaction with electron-rich benzaldehydes to give (E)-1,3-diarylpropenes in high yield.

The structurally related PM-94128 and Ajudazols A and B exhibit differing biological activities but share the isocoumarin core structure. PM-94128 belongs to a large family of compounds known as the aminodihydroisocoumarins and was isolated in 1997. It has been shown to be an inhibitor of DNA and RNA synthesis and have potent cytotoxic activity in vivo. The Ajudazols A and B were isolated in 2004 and have antifungal activity against several important food spoilers. The work that follows details the design and development of a novel method for the generation of the isocoumarin core from isobenzofuran utilizing the Achmatowicz rearrangement of a-hydroxyisobenzofurans. Spirocyclic pyrans such as Polymaxenolide are structurally complex molecules, containing large amounts of functionality. The biological activity of Polymaxenolide is unknown and there have been no total syntheses reported to date.