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Hak-fun Chow. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1981. / Bibliography: leaves 70-73.

He, Xiao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 75-83). / Abstracts in English and Chinese. / Acknowledgement --- p.I / Abstract --- p.II / 摘要 --- p.III / Abbreviation --- p.IV / List of Compounds --- p.VI / List of Figures --- p.VII / Contents --- p.IX / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Transition Metal-Carboranyl Complexes --- p.2 / Chapter 1.1.1 --- Late Transition Metal-Carboranyl Complexes --- p.2 / Chapter 1.1.2 --- Early Transition Metal-Carboranyl Complexes --- p.6 / Chapter 1.2 --- Transition Metal-Carboryne Complexes --- p.12 / Chapter 1.3 --- Five-Membered Heterocycles Incorporating Main Group Elements --- p.20 / Chapter 1.3.1 --- Synthesis and Reactivity of Boroles --- p.20 / Chapter 1.3.2 --- Synthesis and Reactivity of Phospholes --- p.24 / Chapter 1.3.3 --- Synthsis and Reactivity of Silole --- p.28 / Chapter 1.4 --- Our Objectives --- p.31 / Chapter Chapter 2 --- Nickelacycles Incorporating a Carboranyl Unit --- p.32 / Chapter 2.1 --- Introduction --- p.32 / Chapter 2.2 --- "Synthesis, Characterization and Reactivity of Nickelacycles Bearing (2-CPh2O-l,2-C2B10H10)2-Ligand" --- p.32 / Chapter 2.2.1 --- Synthesis and Characterization --- p.32 / Chapter 2.2.2 --- Reactivity Study --- p.34 / Chapter 2.2.3 --- X-ray Structure --- p.36 / Chapter 2.3 --- "Synthesis and Characterization of Nickelacycles Bearing [2-C(Ph)=N-l,2-C2B10H10]2- Ligand" --- p.44 / Chapter 2.3.1 --- Synthesis and Characterization --- p.44 / Chapter 2.3.2 --- X-ray Structure --- p.45 / Chapter Chapter 3 --- Five-membered Heterocycles of Main Group Elements Incorporating a Carboranyl Unit --- p.47 / Chapter 3.1 --- Synthesis and Characterization of Heterocycles Bearing Phosphorus Element --- p.47 / Chapter 3.2 --- Synthesis and Characterization of Heterocycles Bearing Silicon Element --- p.53 / Chapter 3.3 --- Synthesis and Characterization Heterocycles Bearing Boron Element --- p.58 / Chapter Chapter 4 --- Conclusion --- p.61 / Chapter Chapter 5 --- Experimental Section --- p.63 / References --- p.75 / Appendix --- p.84 / Chapter I. --- Crystal Data and Summary of Data Collection and Refinement --- p.84 / Chapter II. --- X-ray crystallographic data in CIF (electronic form)

M.Sc. (Chemistry) / Inhibition of mycothiol biosynthesis pathway has attracted attention from chemists and biochemists who aim to develop novel anti-TB drugs. A possible route to inhibit the production of mycothiol in cells may be via the inhibition of enzymes involved in the biosynthetic pathways. Molecular analogues that mimic mycothiol and containing tetrahedral-forming functional groups have been reported to show activity against mycothiol biosynthesis by inhibiting the enzymes in the mycothiol biosynthetic pathway...

Activated dichloro- and difluoro- monomers are well known for the synthesis of high-performance polymeric materials through the use of aromatic nucleophilic displacement reactions. Here, novel activated difluoro monomers were synthesized using the well established chemistry of Reissert compounds. Difunctional bis(Reissert compound)s were synthesized by the reaction of 4-(pfluorobenzylisoquinoline) and trimethylsilyl cyanide with the following diacid chlorides: sulfonylbis(p-phenyleneoxy)dibenzoy chloride, oxybis (benzoyl chloride), and sulfonylbis(benzoyl chloride}. These aforementioned compounds were rearranged using NaH/THF to produce the desired diketones. Finally, difluorotetraketone monomers were produced by oxidation of the benzylic methylenes of the diketones. These reactions were evaluated by FTI R and 1 HNMR. These new activated heterocyclic difluorotetraketones are precursors to novel heterocyclic poly(ether ketones). / Master of Science

The chemistry of a well established class of compounds, known as Reissert compounds, was used to prepare several novel N-heterocyclic polymers. Initially, alkylation of quinoline Reissert compounds was closely examined to test the feasibility of the use of such compounds as difunctional monomers. An A-B and an A-A monomer were then prepared by the reaction of quinoline with p-formylbenzoyl chloride and isophthaloyl chloride, respectively. The former monomer could be polymerized interfacially to afford a low molecular weight polyester exhibiting Tg of 190°C. Several novel bis-isoquinolines were prepared using an en amine reaction reported by Minter and Re.52 One of these bis-isoquinolines was used to prepare two novel bis-Reissert compounds which could be polymerized with several dialdehydes to obtain high molecular weight N-heterocyclic polyesters. Cleavage of the ester groups afforded a novel N-heterocyclic polyalcohol. It was observed that circumvention of a rearrangement reaction particular to Reissert compounds by molecular design led to the synthesis of N-heterocyclic polyesters that had the highest molecular weights and intrinsic viscosities. A novel N-heterocyclic difluorodiketone was prepared in four steps using the enamine reaction of Minter and Re52 and Reissert compound chemistry. The diketone was polymerized via standard techniques 72 to afford several novel poly(N-heteroaryl-ether-ketones) with high glass transition temperatures and thermal stabilities. Thus, polymerization of 1,4-bis(4-fluorobenzoyl)isoquinoline with biphenol yielded a poly(ether-ketone) with an intrinsic viscosity of 0.34 dl/g. This polymer showed Tg at 209°C and was stable up to 500°C in air. / Master of Science

Thesis (MSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Cancer is the leading cause of death on the planet, killing an estimated 8.2 million people in the year of 2012.The disease is associated with two families of genes, namely oncogenes and tumour suppressor genes. The hallmarks of cancer pathogenesis include gene amplification, point mutations or chromosomal rearrangements within these genes. Kinases are responsible for the reversible phosphorylation of proteins, which plays a significant and extensive role in cellular signal transduction. Aberrant kinase activity provokes overexpression, mutations and chromosomal translocation and results in the onset of onco- and tumorogenesis, ultimately leading to cancer. Inactivation of this class of enzyme is thus critical as it would result in the suppression of these unwanted activities. For this, researchers have developed kinase inhibitors, specifically targeting these proteins and thus inhibiting signal transduction pathways and tumour growth. This has resulted in great successes, particularly in the case of the commercial inhibitor, imatinib. However, resistance to approved therapeutic agents through mutations has resulted in the search for more potent and selective inhibitors to overcome these obstacles. This project involved the synthesis of bioactive heterocycles linked to 1,2,3-triazoles using either a C-C or C-N bond forming strategy. The synthetic methodology followed included the use of Sonogashira coupling reactions between3-bromoquinoline, 7-chloro-4-iodoquinoline, 4-bromoisoquinolineand5-bromoisoquinolineand trimethylsilylacetylene (TMSA), followed by deprotection of the TMS group to yield heterocycles bearing terminal alkynes. The synthesis of both benzyl azide and 2-(azidomethyl)pyridine as azide fragments, allowed for subsequent coupling of the synthesized azide and alkyne fragments through copper-mediated click chemistry, affording a library of 1,4-substituted 1,2,3-triazole based reversible kinase inhibitors. Synthesis of a second library of o-, m- and p-substituted nitro benzyl azides, allowed for both copper- and ruthenium-mediated click reactions, between the alkynes and nitro benzyl azides synthesized, to yield 1,4- and 1,5-substituted 1,2,3-triazoles, respectively. Finally, reduction of the incorporated o-, m- and p- substituted nitro group, and acylation of the resultant amine with acryloyl chloride, resulted in the incorporation of the important Michael acceptor moiety required for irreversible inhibition. This afforded a library of both reversible and potential irreversible triazole-based kinase inhibitors through efficient copper- and ruthenium-mediated click chemistry. Biological screening and activity assays against the wildtype, and two mutated forms of the EGFR kinase, were undertaken with these synthesized compounds.A number of synthesized inhibitors showed good selectivity for the mutated forms of the EGFR kinase only.The most potent inhibitor N-{2-{[4-(isoquinolin-4-yl)-1H-1,2,3-triazol-1-yl]methyl}phenyl}acrylamide,displayed efficacy in the low μM range - comparable to that of the FDA approved drug, gefitinib. The synthetic methodology derived in this project could be applied to the use of biological space probes with further investigatory research. Furthermore, from the biological screening results obtained, and the selectivity profile shown by these inhibitors, the synthesis of a second generation library of compounds is an additional research possibility. / AFRIKAANSE OPSOMMING: Kanker is die hoof oorsaak van sterftes ter wêreld, wat verantwoordelik is vir die dood van ongeveer 8.2 miljoen mense in die jaar 2012. Die siekte word geassosieer met twee geenfamilies, naamlik onkogene en gewasonderdrukkingsgene. Die kenmerke van kanker pathiogene behels geenversterking, puntmutasies of chromosomale herrangskikking binne in die gene. Kinase is verantwoordelik vir die omkeerbare fosforilering van proteine wat 'n uiters belangrike rol in sellulere sein transduksie speel. Abnormale kinase aktiwiteit lei tot ooruitdrukking, mutasies en chromosomale translokasie wat tot die ontwikkeling van onko- en gewasgroei en wat eindelik tot kanker lei. Deaktivering van die klas van ensieme is dus krities want dit sal die ongewenste abnormale aktiwiteite onderdruk. As gevolg van die bogenoemde, het navorsers kinase inhibeerders ontwikkel wat die spesifieke protein teiken en hiermee die sein transduksie roete asook gewas groei inhibeer. Hiermee het die sukses van inhibeerders veral die kommersiele inhibeerder, imatinib, grootliks toegeneem. Oor die afgelope jare het die belangstelling in die ontwikkeling van meer selektiewe en kragtige inhibeerders toegeneem as gevolg van die weerstand wat goedgekeurde terapeutiese middels opbou. In hierdie projek is daar gebruik gemaak van 'n C-C of C-N bindingsvorming strategie om bioaktiewe heterosikliese molekules te sintetiseer wat gekoppel is aan 1,2,3-triasool funksionele groepe. Die sintetiese metode maak gebruik van Sonogashira reaksies vir die 3-bromo-kwinolien, 7-chloro-4-iodokwinolien, 4-bromoisokwinolien en 5-bromoisokwinolien met trimetielsilielasetileen (TMSA), gevolg met die ontskerming van die TMS-groep om die terminale alkyn op die heterosiklusse te ontbloot. Die asied fragmente, bensiel asied en 2-(asidometiel)piridien, was toe gesintetiseer om met die gevormde heterosiklus alkyne 'n koper ondersteunende kliek chemie te ondergaan. 'n Reeks van 1,4-digesubstitueerde 1,2,3-triasool gebaseerde omkeerbare kinase inhibitore is toe gevorm. 'n Tweede reeks met o-, m-, en p- gesubtitueerde nitro bensiel asiede was gesintetiseer om 1,4- en 1,5- digesubtitueerde 1,2,3-triasole te sintetiseer met behulp van koper- en ruthenium ondersteunende kliek chemie. Laastens was die o-, m-, en p- nitro groepe gereduseer om 'n primêre amien te vorm. Die gevormende amien het 'n asileringsreaksie met akriloïel chloried ondergaan om die kern, die Michael akseptor, te inkorporeer. Die Michael akseptor word benodig om 'n onomkeerbare inhibitoriese aktiwiteit te kan uitvoer. Die projek het dus met behulp van kliek chemie, twee 1,2,3-triasool reekse gelewer wat omkeerbare en onomkeerbare inhibitoriese aktiwiteit kan uitvoer. Die verbindings gesintetiseerd in hierdie projek het keuringstoetse ondergaan teen die wilde tipe en teen twee gemuteerde forme van die EGFR kinase ensiem. Van hierdie verbindings het goeie selektiwiteit vertoon teenoor die gemuteerde EGFR kinase ensiem. Die mees aktiewe inhibeerder, N-{2-{[4-isokwinolin-4-iel)-1H-1,2,3-triasool-1-iel]feniel}akrielamied, het aktiwiteit in die lae μM reeks vertoon. Dié inhibisie waarde is vergelykbaar met die FDA goedgekeurde medikasie, gefitinib. In hierdie projek is sintetiese metodes ontwikkel wat toegepas kan word op meer intensiewe biologiese ondersoeke en asook meer navorsing. Die resultate vekry van die biologiese aktiwiteit, asook die verbindings se selektiwiteit, gee die moontlikheid vir die ontwikkeling en sintese van 'n tweede generasie verbindings.

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

The research in this thesis describes an asymmetric pericyclic cascade approach to the synthesis of a range of enantioenriched oxindoles using enantiopure oxazolidine derived nitrones and disubstituted ketenes. Chapter 1 aims to place this work in the context of the literature, describing other commonly employed or state-of-the-art asymmetric approaches to oxindoles and related compounds. Examples of where these approaches have been used successfully in the total synthesis of related indole alkaloids are also presented. The conception of this project within the group is also described alongside initial attempts to develop the first enantioselective variant of the same reaction using nitrone chiral auxiliaries. Chapter 2 details the optimisation of this asymmetric oxindole forming reaction by structural variation of the nitrone component, culminating in the preparation of an N-TIPBS nitrone based on an oxazolidine framework, which proved to be optimal for this process. Also detailed are attempts to gain insight towards the mechanism of this transformation and to understand the mode of chirality transfer. Chapter 3 details the use of the N-TIPBS nitrone scaffold as a transmitter of chiral information in the synthesis of 3-alkyl-3-aryloxindoles and spirocyclic oxindoles. Chapter 4 delineates the mechanism of this transformation as a pericyclic cascade process. The key stereo-determining features are discussed including the conformational preferences of such chiral oxazolidine derived nitrones and the influence of the N-protecting group on the stereochemical outcome. Synthetic endeavours to provide evidence as to the validity of this computational mechanistic rationale are also presented. Chapter 5 describes regioselectivity studies, and tolerance of both the racemic and asymmetric reactions to varying substitution on the nitrone N-aryl ring. Initial studies were undertaken using achiral nitrones before the interplay between regio- and stereoselectivity was explored, initially with enantiopure N-Boc Garner's aldehyde derived nitrones, and further with N-TIPBS nitrones. Chapter 6 initially describes attempts to transform this chiral auxiliary methodology into a catalytic asymmetric protocol, by investigating in situ ketene formation via various strategies including activation of carboxylic acids. Also described are investigations into related nitrone-ketenimine cycloadditions, and related [3+2] nitrone cycloadditions. Chapter 7 describes the application of this methodology toward the synthesis of compounds with biological relevance. The concise asymmetric synthesis of a Roche anti-cancer agent is outlined, as is the extension of this methodology to the synthesis of indole alkaloid-like species. Finally, the attempted application of this methodology toward the asymmetric synthesis of (+)-gliocladin C is outlined.

Briareum asbestinum, a soft coral, is a rich source of diterpenoid natural products. The secondary metabolites of B. asbestinum fall into four classes : asbestinins, briarellins, briareolate esters, and briaranes. Briareolate esters have been shown to possess biological activity and were previously only reported from Tobago. Our group recently isolated briareolate esters from a specimen collected off the coast of Boca Raton, Florida. To determine whether location has an impact on the chemistry produced by the organism, a method to discern between chemotypes was sought. Several techniques including thin layer chromatography (TLC), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and sclerite analysis were employed, with NMR being the most successful method. By utilizing both 1H and COSY NMR experiments, it is possible to differentiate between the chemotypes of B. asbestinum. Application of this method allowed analysis of chemical variability with respect to location. / by Melody D. Rondeau. / Thesis (M.S.)--Florida Atlantic University, 2012. / Includes bibliography. / System requirements: Adobe Reader. / Mode of access: World Wide Web.