Thesis advisor: James P. Morken / This dissertation will discuss in depth four main projects pertaining to the synthesis and utility of organoboronates for the construction of enantioenriched small molecules. First, reaction optimization and substrate scope expansion of the platinum-catalyzed enantioselective diboration of alkenes are reported. Based on extensive experimental and computational mechanistic analysis, a preliminary stereochemical model is also proposed. A practical boron-Wittig reaction is presented in which synthetically challenging di- and trisubstituted vinyl boronates can be accessed in a highly stereoselective fashion from readily available starting materials. The enantioselective diboration of cis- and trans-vinyl boronates furnished novel 1,1,2-tris(boronate) esters in up to 95:5 er. The intermediate tris(boronate) esters were employed successfully in deborylative alkylations to furnish enantioenriched internal vicinal bis(boronates) in excellent diasteoselectivity. In the final chapter, an enantioselective palladium-catalyzed intramolecular Suzuki-Miyaura coupling between allyl boronates and aryl electrophiles is disclosed. The newly developed transformation provides enantioenriched 5, 6, and 7-membered carbocycles in up to 93:7 er. / Thesis (PhD) — Boston College, 2015. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Marc L. Snapper / Chapter 1. Review of concept and methodology development for asymmetric allylation of carbonyls and imines. Chapter 2. Description of the catalytic asymmetric addition of allyltrichlorosilane to aldehydes catalyzed by a proline-based N-oxide catalyst. Chapter 3. Introduction of the first catalytic asymmetric silylation of alcohols for desymmetrization of meso-diols. Chapter 4. Presentation of asymmetric silylation for synthesis of chiral syn-1,2-diols by kinetic resolution or divergent reaction on a racemic mixture. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

M.Sc.(Med.), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Knowledge of the predominant agents associated with CAP locally is essential, as it represents the basis for empiric antibiotic treatment. The objective of this study was to establish polymerase chain reaction (PCR)-based methods that could be used to identify CAP pathogens. Real-time PCR assays were developed to detect 10 viral and 5 non-viral pathogens as well as 2 internal controls using SYBR Green I and TaqMan probes, in singleplex and multiplex reactions. Six multiplex assays, with sensitivities of 1-10 copies/μl, were successfully developed to simultaneously detect 12 organisms. These reactions were used to test a limited number of patient and simulated samples. Data from the real-time PCR methods compared favourably to those from commercially available conventional PCR kits. These detection methods could be used to complement each other in prevalence studies and in selected diagnostic applications.

Le développement d’une chimie propre et donc durable est un des challenges majeurs du 21ème siècle dans les pays industrialisés. Étant au cœur de nombreuses découvertes dans divers domaines scientifiques allant de la physique à la médecine, les sciences chimiques doivent jouer un rôle central pour résoudre un certain nombre de problèmes environnementaux auxquels nous devons faire face. Mon travail de thèse s’inscrit dans cette problématique par le développement de méthodologies de synthèse faisant intervenir plusieurs transformations dans le même réacteur. Nous avons notamment développé des séquences réactionnelles appelées HRC (pour Heck-Reduction-Cyclization, en anglais) prenant appui sur le caractère multi-tâche d’un catalyseur à base de palladium. Ces travaux nous ont permis de préparer une grande variété d’hétérocyles ou composés fonctionnalisés parmi lesquels nous pouvons citer les oxindoles, les indanones, ou encore les naphthoxindoles. Ces travaux ont donné lieu pour le moment à quatre publications dans des journaux à comité de lecture. / The development of clean chemistry and therefore sustainable is one of the major challenges of the 21st century in industrialized countries. Being in the heart of many discoveries in various scientific fields ranging from physics to medicine, the chemical sciences must play a central role in solving a number of environmental problems we face. My thesis work is part of this problem through the development of synthetic methodologies involving several transformations in the same reactor. We have developed the reaction sequences called HRC (for Heck-Reduction-cyclization) building on the multi-task of a palladium catalyst. This work allowed us to prepare a variety of functionalized heterocycles or compounds from which we can cite the oxindole, the indanones, or the naphthoxindoles. This work has resulted for the time four publications in peer-reviewed journals.

University of Macau / Institute of Chinese Medical Sciences

We report the development of a general route to the synthesis of [4.3.1], [3.3.1], an especially [3.2.1] bicyclic compounds structurally related to vitisinol D, a natural product. This allows for diastereoselective synthesis of bicyclic compounds with five adjacent chiral centers. This route was employed in a preliminary SAR investigation into the neuroprotectant effect of small molecules in an in vivo experiment measuring the degree of restorative effect of synaptic transmission in the neuromuscular junction of Drosophila melanogaster larvae under acute oxidative stress. One of the compounds exhibited intriguing potential as a neuroprotectant and outperformed resveratrol in restoring synaptic function under oxidative stress. The hypothesis that bridged bicyclic compounds may hold promise as drug scaffolds due to their conformational rigidity and ability to orient functional appendages in unique orientations is developed. The second focus is a mechanistic investigation into a tetrabutylammoniumcatalyzed cycloaddition as evidence of a novel ammonium-alkyne interaction. A carbamate nitrogen adds to a non-conjugated carbon–carbon triple bond under the action of an ammonium catalyst leading to a cyclic product. Studies in homogeneous systems suggest that the ammonium agent facilitates cyclitive nitrogen–carbon bond formation through a cation–π interaction with the alkyne unit. Using Raman spectroscopy, this cation–π interaction is directly observed for the first time. DFT modeling elucidated the mechanistic factors in this cycloaddition. A teaching experiment was developed based on this mechanistic investigation. Control experiments were employed to demonstrate the testing of two alternative mechanistic hypotheses. Cyclization reactions were performed with a soluble base (sodium phenoxide) with and without tetrabutylammonium bromide under homogeneous conditions. Students observed that ammonium salt accelerates the reaction. They were encouraged to develop a testable hypothesis for the role of the ammonium salt in the cyclization mechanism: typical phase transfer or other. IR spectroscopy was used to directly observe a dose dependent shift of the alkyne stretching mode due to a cation−π interaction. Undergraduates were able to employ the scientific method on a contemporary system and see how data are generated and interpreted to adjudicate between rival hypotheses in a way that emulates authentic and current research in a lab setting. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

by Ivan H.F. Chung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 63-67). / Acknowledgements --- p.i / Contents --- p.ii / Abstract --- p.iv / Abbreviations --- p.v / Chapter Chapter I --- Introduction / Chapter I-1. --- General background --- p.1 / Chapter I-2. --- Asymmetric Diels-Alder reaction using chiral auxiliaries --- p.2 / Chapter I-2A --- Some well-known chiral auxiliaries --- p.3 / Chapter I-2B --- Carbohydrates as chiral auxiliaries --- p.6 / Chapter I-3. --- Asymmetric Diels-Alder reaction using chiral catalysts --- p.10 / Chapter Chapter II --- Results and Discussion --- p.14 / Chapter II-1. --- "Synthesis of η6-(benzyl 2-O-acryloyl-3,4-O-isopropylidene- β-L-arabinopyranoside) tricarbonylchromium(O) (47)" --- p.15 / Chapter II-2. --- "Syntheses of 4'-methylbenzyl 2-O-acryloyl-3,4-O- isopropylidene-β-L-arabinopyranoside (57) and η6-(4'- methylbenzyl 2-O-acryloyl-3,4-O-isopropylidene-β-L- arabinopyranoside) tricarbonylchromium(O) (56)" --- p.19 / Chapter II-3. --- "Syntheses of naphthylmethyl 2-O-acryloyl-3,4-O- isopropylidene-α-L-arabinopyranosides" --- p.22 / Chapter II-4. --- Diels-Alder reaction using the dienophiles 56 and 57 as the chiral auxiliaries --- p.25 / Chapter II-5. --- "Synthesis of benzyl 3,4-O-methylene-β-L-arabinopyranoside (81)" --- p.32 / Chapter II-6. --- Using the alcohol 81 as the ligand for Lewis acid in the Diels-Alder reaction --- p.36 / Chapter Chapter III --- Conclusions --- p.38 / Chapter Chapter IV --- Experimental Section --- p.40 / Chapter IV-1. --- Experimental section for the asymmetric Diels-Alder reaction using the chiral auxiliaries --- p.41 / Chapter IV-2. --- Experimental section for the asymmetric Diels-Alder reaction using the chiral catalysts --- p.59 / References --- p.63 / List of spectra --- p.68

Eva Tsui Yuen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 124-140). / SUMMARY / ACKNOWLEDGEMENT / Chapter CHAPTER I --- INTRODUCTION --- p.1 / Chapter CHAPTER II --- LITERATURE REVIEWS --- p.5 / Chapter 2.1 --- Anatomy and Histology of Uterine Cervix --- p.6 / Chapter 2.2 --- Premalignant and Malignant Lesions of Uterine Cervix --- p.9 / Chapter 2.2.1 --- Incidence --- p.9 / Chapter 2.2.2 --- Etiological Factors --- p.10 / Chapter 2.2.3 --- Classification and Histopathology --- p.13 / Chapter A. --- Condyloma --- p.13 / Chapter B. --- Cervical Intraepithelial Neoplasia (CIN) --- p.16 / Chapter C. --- Microinvasive Squamous Cell Carcinoma --- p.19 / Chapter D. --- Invasive Squamous Cell Carcinoma --- p.22 / Chapter E. --- Adenosquamous Carcinoma --- p.25 / Chapter F. --- Adenocarcinoma --- p.26 / Chapter 2.3 --- Human Papillomavirus (HPV) --- p.28 / Chapter 2.3.1 --- Organization of the Viral Genome --- p.28 / Chapter 2.3.2 --- Classification --- p.35 / Chapter 2.4 --- The Impact of Human Papillomavirus (HPV)in Premalignant and Malignant Lesions of Uterine Cervix --- p.35 / Chapter 2.5 --- Cervical Screening --- p.40 / Chapter 2.5.1 --- Cervical Smear --- p.40 / Chapter 2.5.2 --- Cervicography --- p.41 / Chapter 2.5.3 --- HPV Detection --- p.43 / Chapter CHAPTER III --- MATERIALS AND METHODS --- p.54 / Chapter 3.1 --- Study Population --- p.55 / Chapter 3.2 --- Specimen Collection --- p.56 / Chapter 3.3 --- Extraction of Genomic DNA --- p.56 / Chapter 3.4 --- Polymerase Chain Reaction (PCR) --- p.60 / Chapter 3.4.1 --- Oligonucleotide Primers and Positive Controls --- p.60 / Chapter 3.4.2 --- Polymerase Chain Reaction Procedure --- p.62 / Chapter A. --- PCR Optimization --- p.62 / Chapter B. --- Multiplex PCR --- p.63 / Chapter C. --- Single Primer PCR --- p.64 / Chapter 3.4.3 --- Gel Electrophoresis --- p.65 / Chapter 3.5 --- Southern-blot and Hybridization --- p.69 / Chapter 3.5.1 --- Southern-blot --- p.69 / Chapter 3.5.2 --- Nucleic Acid Hybridization --- p.71 / Chapter A. --- Oligonucleotide Probes --- p.71 / Chapter B. --- Radioactive Labelling of Probes --- p.73 / Chapter C. --- Hybridization --- p.74 / Chapter D. --- Removal of Labelled Probes --- p.77 / Chapter CHAPTER IV --- RESULTS --- p.78 / Chapter 4.1 --- Cytological Findings of Cervical Scrapes --- p.79 / Chapter 4.1.1 --- Colposcopy Group --- p.79 / Chapter 4.1.2 --- General Gynaecology Group --- p.81 / Chapter 4.1.3 --- Antenatal Group --- p.81 / Chapter 4.2 --- PCR Optimization --- p.84 / Chapter 4.3 --- Detection of HPV DNA by Multiplex PCR --- p.86 / Chapter 4.3.1 --- Colposcopy Group --- p.86 / Chapter 4.3.2 --- General Gynaecology Group --- p.89 / Chapter 4.3.3 --- Antenatal Group --- p.91 / Chapter 4.4 --- Detection of HPV DNA by Southern-blot Hybridization --- p.91 / Chapter 4.5 --- Detection of HPV DNA by Single Primer PCR --- p.104 / Chapter CHAPTER V --- DISCUSSION --- p.110 / Chapter CHAPTER VI --- CONCLUSION --- p.121 / REFERENCES --- p.124

by Graham Neil Thomas. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 167-191). / Abstract --- p.i / Contents --- p.iii / List of tables --- p.viii / List of figures --- p.x / Abbreviations --- p.xi / Acknowledgements --- p.xiii / Chapter Chapter 1 - --- Introduction / Chapter 1.1 --- Introduction to the genus rotavirus --- p.1 / Chapter 1.2 --- General characteristics of rotavirus --- p.3 / Chapter 1.3 --- Clinical and epidemiological characteristics of rotaviral infections --- p.4 / Chapter 1.3.1 --- Clinical features of rotavirus infection --- p.4 / Chapter 1.3.2 --- Nosocomial rotavirus infection --- p.4 / Chapter 1.3.3 --- Morbidity and Mortality of rotavirus diarrhoea --- p.5 / Chapter 1.3.3.1 --- Seasonal distribution of rotavirus in temperate regions … --- p.5 / Chapter 1.3.3.2 --- Rotavirus infections in developing countries --- p.6 / Chapter 1.3.3.3 --- Rotavirus infections in developed countries --- p.6 / Chapter 1.3.4 --- Host Resistance to rotavirus infection --- p.7 / Chapter 1.3.5 --- Pathogenesis --- p.9 / Chapter 1.4 --- Vaccine development in rotavirus prevention --- p.10 / Chapter 1.4.1 --- Attenuated HRV as candidate vaccine strains --- p.11 / Chapter 1.4.2 --- Animal RV candidate vaccine strains (Jennerian approach)..… --- p.11 / Chapter 1.4.3 --- Intra- and interspecies reassortants vaccine strains --- p.12 / Chapter 1.4.4 --- Passive immunisation --- p.13 / Chapter 1.5 --- Laboratory diagnosis of rotavirus infections --- p.14 / Chapter 1.5.1 --- Detection of rotavirus --- p.14 / Chapter 1.5.2 --- Negative stain electron microscopy (EM) --- p.15 / Chapter 1.5.3 --- Immunological assays for the detection of rotavirus antigens --- p.15 / Chapter 1.5.4 --- Polyacrylamide gel electrophoresis (PAGE) of RV RNA --- p.16 / Chapter 1.5.5 --- Nucleic acid probe hybridisation assays --- p.17 / Chapter 1.6 --- Antigenic classification of rotaviruses --- p.17 / Chapter 1.6.1 --- Rotavirus groups --- p.17 / Chapter 1.6.2 --- Rotavirus subgroups --- p.18 / Chapter 1.6.3 --- Rotavirus serotypes --- p.19 / Chapter 1.6.4 --- Rotavirus genogroups --- p.21 / Chapter 1.7 --- Molecular biology of rotavirus --- p.21 / Chapter 1.7.1 --- Rotavirus genomic organisation --- p.21 / Chapter 1.7.2 --- Gene coding assignments --- p.22 / Chapter 1.7.3 --- Genome and protein structure of rotavirus VP7 --- p.22 / Chapter 1.8 --- Reverse transcriptase-Polymerase chain reaction (RT-PCR) for the genotyping of rotavirus --- p.32 / Chapter 1.8.1 --- Prevention of contamination in RT-PCR --- p.34 / Chapter 1.9 --- Objectives of the study --- p.36 / Chapter Chapter 2 - --- Methods / Chapter 2.1 --- Collection of specimens --- p.38 / Chapter 2.2 --- Standard rotavirus strains --- p.38 / Chapter 2.3 --- Tissue culture techniques --- p.39 / Chapter 2.3.1 --- Growth of MA104 cell line --- p.39 / Chapter 2.3.2 --- Subculturing of MA104 cell line --- p.40 / Chapter 2.3.3 --- Virus propagation and isolation --- p.40 / Chapter 2.3.4 --- Harvesting and purification of viral particles --- p.41 / Chapter 2.4 --- Rotavirus electropherotyping by PAGE --- p.42 / Chapter 2.4.1 --- RNA extraction --- p.42 / Chapter 2.4.2 --- Polyacrylamide gel electrophoresis (PAGE) --- p.43 / Chapter 2.4.3 --- Silver staining of RNA in polyacrylamide gels --- p.43 / Chapter 2.5 --- Enzyme immunoassays in rotavirus typing --- p.44 / Chapter 2.5.1 --- Preparation of monoclonal antibodies (mAb) from hybridoma cell lines --- p.44 / Chapter 2.5.1.1 --- Growth of hybridoma cell lines --- p.44 / Chapter 2.5.1.2 --- Preparation of the ascitic fluid - monoclonal Abs --- p.45 / Chapter 2.5.2 --- Confirmation of mAb activity by immunofluorescence (IF)..… --- p.46 / Chapter 2.5.2.1 --- Preparation of virus-infected cells --- p.46 / Chapter 2.5.2.2 --- Confirmation of the serotype specificity of the mAb by immunofluorescence microscopy --- p.47 / Chapter 2.5.3 --- Polyclonal hyperimmune antisera against rotavirus --- p.48 / Chapter 2.5.4 --- Immunoglobulin purification --- p.48 / Chapter 2.5.5 --- Monoclonal antibody-based serotyping and subgrouping EIA --- p.49 / Chapter 2.6 --- Reverse transcription-Polymerase Chain Reaction genotyping of rotavirus (RT-PCR) --- p.53 / Chapter 2.6.1 --- Primers used in RT-PCR --- p.53 / Chapter 2.6.1.1 --- Preparation of oligonucleotide primers for RV genotyping --- p.53 / Chapter 2.6.1.2 --- Detachment of the oligonucleotide from the column --- p.54 / Chapter 2.6.1.3 --- Purification of the oligonucleotides --- p.55 / Chapter 2.6.1.4 --- Confirmation of oligonucleotide synthesis --- p.58 / Chapter 2.6.2 --- Preparation of specimens --- p.59 / Chapter 2.6.3 --- Reverse transcription of genomic RNA template and PCR…… --- p.64 / Chapter 2.6.4 --- PCR genotyping using full-length cDNA template --- p.64 / Chapter 2.6.5 --- Product identification --- p.65 / Chapter Chapter 3 - --- Results / Chapter 3.1 --- Epidemiology of rotavirus infections in Hong Kong --- p.70 / Chapter 3.2 --- RT-PCR genotyping of rotavirus --- p.74 / Chapter 3.3 --- Seasonal distribution of rotavirus genotypes --- p.76 / Chapter 3.4 --- Comparison of RT-PCR genotyping of the VP7 gene with mEIA…… --- p.79 / Chapter 3.5 --- Relationship between electropherotyping and genotyping by RT-PCR --- p.91 / Chapter 3.6 --- Atypical rotavirus strains --- p.92 / Chapter 3.7 --- Specimens exhibiting multiple genotype specificities --- p.93 / Chapter 3.8 --- HRV RT-PCR genotype primers --- p.95 / Chapter Chapter 4 - --- Discussion / Chapter 4.1 --- Epidemiology of rotavirus infections in Hong Kong --- p.101 / Chapter 4.2 --- RT-PCR genotyping of rotavirus --- p.103 / Chapter 4.2.1 --- Modifications to methodology --- p.104 / Chapter 4.2.2 --- Rotavirus genotypes --- p.107 / Chapter 4.3 --- Comparison of RT-PCR genotyping with mEIA typing --- p.111 / Chapter 4.4 --- Relationship between electropherotyping and RT-PCR genotyping --- p.113 / Chapter 4.5. --- Rotavirus genotype distribution in Hong Kong --- p.115 / Chapter 4.6 --- Specimens containing atypical rotavirus strains --- p.119 / Chapter 4.7 --- Stool specimens exhibiting multiple rotavirus genotypes identified by RT-PCR --- p.122 / Chapter 4.8 --- Specificity analysis of RT-PCR primers --- p.124 / Chapter 4.8.1 --- 5non-coding region (1-28) - primer BEG9 --- p.125 / Chapter 4.8.2 --- 3non-coding region (1033/6-1062) - primers END9/RVG9. --- p.125 / Chapter 4.8.3 --- Variable region A (165-198) - primer aAT8 (G8) --- p.125 / Chapter 4.8.4 --- Variable region B (309-351) - primer aBT1 (G1) --- p.126 / Chapter 4.8.5 --- Variable region C (408-438) - primer aCT2 (G2) --- p.127 / Chapter 4.8.6 --- Variable region D (477-504) - primer aDT4 (G4) --- p.127 / Chapter 4.8.7 --- Variable region E (672-711) - primer aET3 (G3) --- p.128 / Chapter 4.8.8 --- Variable region F (747-776) - primer aFT9 (G9) --- p.128 / Chapter 4.9 --- Future developments of the study --- p.131 / Appendices / Chapter A1 --- Materials --- p.135 / Chapter A2.1-2.9 --- Distribution of electropherotypes between July 1985 and April 1994 --- p.145 / Chapter A3.1-3.11 --- Individual rotavirus strain electropherotypes --- p.153 / Chapter A4.1-4.8 --- "Comparison of nucleotide sequences for the 3', 5'-non-coding regions and variable regions A to F for the VP7 gene" --- p.158 / Chapter A4.9 --- Rotavirus strains and nucleotide sequence references for the VP7 gene --- p.166 / References

>Magister Scientiae - MSc / This project aimed to investigate proton unbound states in 32Cl using the 32S(3He; t) charge-exchange reaction. This research is relevant both in the context of nuclear structure and astrophysics. Excited states in 32Cl up to Ex 6 MeV were produced using a 50 MeV 3He++ beam from the K200 separated sector cyclotron at iThemba LABS. The triton ejectiles were mass analysed and detected at the focal plane of the K600 magnetic spectrometer. An additional segmented silicon detector array called CAKE was used to detect the unbound protons from states in 32Cl in conjunction with the tritons. In this work we looked for potential sources of isospin admixture that could explain the apparent violation of the Isobaric Multiplet Mass Equation (IMME) for the A = 32, T = 2 quintet. We also investigated the possibility of determining the 31S(p; ) reaction rate indirectly, via measurements of the partial proton widths of unbound states in 32Cl.