Organic Chemistry Commons^™

Synthesis Of Portions Of An Acinetobacter Baumannii Lipooligosaccharide (Los), Brandon Conrad

LSU Doctoral Dissertations

Glycoconjugate vaccines have become an effective strategy for protection against an array of globally persistent diseases resulting from pathogenic bacteria such as Haemophilus influenzae type b (Hib), Neisseria meningitidis, and Salmonella enterica serotype Typhi. Comprised of a carbohydrate (referred to as glycan) covalently inked to a carrier protein, these vaccines can initiate adaptive immunity by inducing B and T cell responses once in the lymphatic system. This is particularly relevant for infants two years of age and younger whose immune systems are not fully developed. A continuously emerging threat in clinical settings, Acinetobacter baumannii is a Gram-negative bacterium …

Novel Approaches To The Activation Of Chalcogenoglycosides For O-Glycosylation, Tiffany Duong

LSU Doctoral Dissertations

Carbohydrates are integral to various biological processes such as cell signaling, function and regulation. Carbohydrates also play critical roles in various disease and metastatic pathways. This has garnered considerable attention to the field of glycoscience, however, the study of carbohydrate-containing compounds remains a challenge due to the difficulty in obtaining pure samples from natural sources. As a result, the biological evaluation of carbohydrates relies on synthetic chemistry to produce pure compounds in significant quantities. However, the synthesis of carbohydrates present their own challenges owing to the complexity in controlling stereochemistry and regiochemistry. The most significant of these challenges is controlling …

Advances In Stereoselective Glycosylation: Electron-Withdrawing Groups, Benzyne-Mediated Stereoinversion, And Visible-Light Photochemistry For 1,2-Cis O-Glycosylation, Erik Giovanni Alvarez Valenzuela

LSU Doctoral Dissertations

The symbiotic relationship between humans and their microbiota is essential for health, with imbalances in the complex microbiota ecosystem linked to a variety of disorders ranging from neurodegenerative to gastrointestinal diseases. Bacteria within the human microbiota, comprising over 1000 known species, are densely and diversely coated with oligosaccharides crucial for functions like cell recognition, communication, signaling, adhesion, proliferation, and pathogenic inhibition. However, studying the structure-activity relationships of these sugars which are also secreted by bacteria is challenging due to difficulties in obtaining homogenous samples from natural sources.

Chemical synthesis offers a solution by enabling the production of well-defined oligosaccharides in …

Examining The Authenticity Of The 'Ether Model' In Certain O-Glycosylation Reactions, Varad Vinayak Agarkar

LSU Doctoral Dissertations

Acinetobacter baumannii is a gram-negative bacterium species that is responsible for nosocomial infections. It has shown antibiotic resistance and has been designated an urgent threat by the CDC. In Chapter 1, I highlight my efforts in the synthesis of a Kdo building block in the journey towards the construction of an A. baumannii lipooligosaccharide (LOS) core pentasaccharide- a potential candidate for glycoconjugate vaccine against A. baumannii infection. I talk about various optimizations and improvements in the Kdo monosaccharide synthesis and the mechanistic insights I provided about a critical transformation in the synthetic sequence.

Chemical O-glycosylation is a significant research …

Molybdenum Alkylidyne Complexes With Phenoxide Ligands For Alkyne Metathesis, Marvin L. Stewart Jr

LSU Doctoral Dissertations

Abstract

Alkyne metathesis is a powerful synthetic tool, which provides easy access to complex organic molecules in a single-step. It is a dynamic covalent reaction that scrambles alkynes, carbon-carbon triple bonds (C≡C). Molybdenum- or tungsten-alkylidyne (Mo≡C, W≡C) complexes are typically used as catalyst to cleave and reform alkyne bonds. Our goal has been to gain a deeper understanding of the intrinsic differences between functional ligands by the development of novel phenoxide ligands.

In chapter 2 we explore the detailed synthesis of novel phenoxide podand ligands in an effort to identify their mo-alkylidyne complexes. We were able to synthesize a variety …

Applied Depositional Geosystems Of The Coos Bay Basin, Oregon: Organic Geochemistry, Maturation, Paleoenvironmental Reconstruction And Biostratigraphy Of The Coaledo Delta During The Middle Eocene Climatic Optimum (Meco), Allison K. Barbato

LSU Doctoral Dissertations

The Coos Bay Basin on the southwestern coast of Oregon is a forearc basin that contains exceptionally preserved Eocene to Miocene, tidal to wave-dominated, shallow deltaic to deep marine sediments of the Coaledo Delta. Coastal depositional environments are known to host source, reservoir, and seal rocks. Climate, topographic relief, and geographical position all play an important role in regional vegetation development and oceanic setting. This study assesses 84 outcrop and 12 core samples from Coos Bay for their organic geochemical characteristics and microfossil assemblage to provide source rock characterization information, organofacies descriptions, environmental reconstructions, and age control.

Results indicate the …

Design, Synthesis And Post Functionalization Of Bodipy Dyes For Use As Chemo Sensors., Caroline Njeri Ndung'u

LSU Doctoral Dissertations

An overview of BODIPYs history, basic structure, electronic properties is described. Additionally, their attribute of tenability in their photophysical and electronic properties has been discussed. Lastly, their application in the biomedical field as bio imaging, labeling, chemo sensors and photosensitizers are also discussed. In Chapter 2, a library of meso- Pyridyl and meso pyridinium BODIPY dyes was designed, synthesis and comparison on their photophysical, electrochemical and cytotoxic studies done. From this study chlorine atoms at the 2, 6 positions was shown to enhance their relative fluorescence quantum yields in different organic solvents and water. In chapter 3, 8(meso)-pyridyl-BODIPYs with a …

Synthesis Of An Acinetobacter Baumannii Lipooligosaccharide Subunit, James M. Armstrong Ii

LSU Doctoral Dissertations

Acinetobacter baumannii is a Gram-negative, multi drug-resistant bacterium that was placed on the World Health Organization’s watchlist of drug-resistant bacteria. A. baumannii is an ESKAPE pathogen, one of six increasingly antimicrobial-resistant bacteria that are responsible for nosocomial infections. Alternative therapies, such as vaccines, are required to decrease the world’s reliance on antimicrobial agents. Specifically, glycoconjugate vaccines such as those used against Haemophilus influenzae B, Streptococcus pneumoniae, and Neisseria meningitidis are used globally and are highly effective. These vaccines consist of an antigenic bacterial glycan bound to a carrier protein. The glycan is usually a capsular polysaccharide (CPS), however, the notion …

Design, Synthesis, And Characterization Of Nqo1-Activatable Luminescent Probes, Ovini Vionika Weeratung Kankanamge

LSU Doctoral Dissertations

Being among the top ten causes of death, cancer has constantly been able to grab the attention of researchers all around the world. While several treatment methods prevail to cure cancer, the seriousness of this medical condition requires continuous work in the development of novel treatments as well as scientific advancements in order to achieve early detection of the disease. Luminescence imaging is an emerging field in both diagnosis of diseases, as well as a means to provide guidance in clinical surgeries. While there exist only a few contrasting agents approved by the Food and Drug Administration, the need for …

Synthesis Of Carbon Nanohoops And Macrocycles Via Alkyne Metathesis, Xin Zhou

LSU Doctoral Dissertations

Cycloparaphenyleneacetylene (CPPA) and cycloparaphenylene (CPP) are called carbon nanohoops; they are fully conjugated macrocycles with radially oriented aromatic groups. Though many syntheses of CPPA and CPP were reported, in the macrocyclization step, the yields were usually not satisfying, as the reactions were irreversible. Our group utilizes alkyne metathesis to address this problem. Chapter 1 provides backgrounds and an introduction to the carbon nanohoops and alkyne metathesis.

Chapter 2 details the synthesis of the [3]CPP⁴A and [3]CPP⁵A, with good macrocyclization yields via alkyne metathesis. This study showed the error-correction ability of alkyne metathesis, especially with nonsymmetric substrates. …

Novel Synthetic Routes To Functionalized Tetrahydrobenzofurans And Chiral A-Quaternary A'-Hydroxy Ketones, Fatimat Oluwayemisi Badmus

LSU Doctoral Dissertations

Various naturally occurring organic compounds possess unique biological activities and have found exclusive applications in pharmaceuticals and agrochemicals. Their undeniable significance has necessitated the discovery and development of novel reactions that unveil advanced chemical transformations. This dissertation will detail our new approaches towards the synthesis of functionalized tetrahydrobenzofurans and chiral α-quaternary α’-hydroxy ketones. The transformations in these approaches were enabled by the chemistries of oxyallyl cations, Grignard reaction and Claisen rearrangement.

Chapter 1 introduces oxyallyl cations, their generation, reactions and applications. Our previous contributions, in the form of silyloxyallyl cations, to solve the regioselective issues associated with unsymmetrical oxyallyl cations …

Development Of 1,2-Cis-Selective Glycosylation Protocols And Multistep Synthesis Of Glycans From Acinetobacter Baumannii., Dancan Kamau Njeri

LSU Doctoral Dissertations

Access to various oligosaccharides has been made possible by glycosylation reactions. This is mainly through chemical synthesis and enzymatic approaches. Herein, I talk about glycosylation through chemical synthesis. In general, glycosylation reactions lead to a mixture of 1,2-cis and 1,2-trans stereoisomers. Stereoselective access to 1,2-trans isomer is highly developed; it efficiently relies on neighboring group participation. However, efficient access to 1,2-cis selective glycosylation is still a work in progress. In Chapter 1, I highlight notable efforts developed so far that address the 1,2-cis selectivity challenge in glycosylation.

In Chapter 2, I demonstrate how I improved …

New Chemoselective Dehydration And Cyclization Strategies Enabled By Triphosgene, Moshood Oreofeoluwa Ganiu

LSU Doctoral Dissertations

Since Friedrich Wöhler’s synthesis of urea in 1828, the techniques of organic synthesis have developed and advanced greatly. This advancement has facilitated the discovery of new organic synthetic methods, and enabled access to a more expansive chemical space. The purpose of this dissertation is to present the development of new organic synthetic reactions that were uncovered through previous discoveries. Additionally, the main theme of this work relies on exploiting the versatility of triphosgene in organic synthesis. To this end, the developed chemistries rely on the ability of triphosgene to serve as an activating agent, and a chloride source.

Chapter 1 …

New Synthetic Reactions Enabled By Protected Oxyallyl And Amidoallyl Cations, Binod Nepal

LSU Doctoral Dissertations

This dissertation entails design and development of two new synthetic methodologies made possible through the generation of cationic species, namely oxyallyl and amidoallyl cations. Chapter 1 involves literature survey on generation and trapping of oxyallyl cations. Mostly known for cycloaddition reactions with these elusive species, the most recent approach of direct nucleophilic capture of oxyallyl cations are discussed. Apt design of substrates and reaction conditions by Kartika Group to access a-electrophilic carbon towards the synthesis of a variety of value-added compounds, i.e., 1,4- and 1,6-dicarbonyls, carbazoles, densely substituted pyrroles and furans are elaborated.

Chapter 2 focuses on our discovery of …

Novel Synthetic Transformations Targeting Δ-Valerolactone And Isocoumarin, Joshua Paul Van Houten

LSU Doctoral Dissertations

The purpose of this dissertation is to describe the efforts undertaken to develop synthetic methodology targeting δ-valerolactone and isocoumarin. At the onset, an introduction to the δ-valerolactone and isocoumarin is given. Relevant examples of δ-valerolactone being utilized in the production of materials of biological and industrial application are then discussed. Following, current methods for forming δ-valerolactone are presented. After, an introduction to isocoumarin is begun. Current methods for producing isocoumarin are then discussed.

The results and discussion section of this dissertation will focus on two methods that were explored with the goal of producing α-acyl-δ-valerolactone with two different substitution patterns. …

Synthesis Of Structurally Diverse Molecular Scaffolds Enabled By Protected Oxyallyl Cations, Joshua Andrew Malone

LSU Doctoral Dissertations

This dissertation focuses on the synthesis of diverse molecular scaffolds through the use of protected oxyallyl cation intermediates. Chapter One provides background on the generation and applications of oxyallyl and silyloxyallyl cations, while focusing on the direct nucleophilic capture of theses intermediates to generate functionalized ketones and silylenolates. Chapter Two depicts our approach to generate six-membered silyloxyallyl cations through the use of mild Brønsted acid activation. Regioselective nucleophilic capture of these intermediates successfully produced diverse a,a’-substituted silylenol ethers enabled by polar solvent and residual water.

Chapter three details strategies to generate 1,4-dicarbonyl compounds, focusing on the capture of cationic intermediates …

Methods For 1,2-Cis-Selective O-Glycosylation And Synthesis Of An A. Baumannii Lipooligosaccharide Core Disaccharide, Ashley Fulton

LSU Doctoral Dissertations

This dissertation focuses on the formation of organic thin films on gold surfaces and synthesis of oligosaccharides. Chapter one, is a brief introduction on the utility of thin films, as well as ways to characterize thin films, as well as, a report on the attempt to form organic thin films on Au(111) surfaces using photoredox catalysis.

Glycoconjugates on cell surfaces serve as important mediators of intercellular recognition, adhesion, and viral infection. Due to the significant role that glycoconjugates play on the surface of cells, oligosaccharide synthesis is of great interest. Chapter two, is an extensive review of oligosaccharide synthesis, its …

New Synthetic Transformations Utilizing Silyloxyallyl Cations And Epoxonium Ions As Reactive Intermediates, Alexander Houston Cleveland

LSU Doctoral Dissertations

The development of new chemical transformations is of paramount importance in organic chemistry. In fact the study and creation of new reactions often uncovers new chemical reactivities and creates a new area of chemistry. The purpose of this dissertation is to present the development of new synthetic reactions that were uncovered through previous discoveries. Additionally the underlying theme of this work relies on the intermediacy of cationic reactive intermediates such as silyloxyallyl cations and epoxonium ions. Chapters 1 and 2 present the reactivity of novel silyloxyallyl cations. These cationic species are generated via the mild ionization of a-hydroxy silylenol ethers …

Hierarchical Conjugated Polymer Systems Prepared By Controlled Chain-Growth Polymerization, Chunwa Peter Kei

LSU Doctoral Dissertations

π-Conjugated polymer materials may have a significant economic impact on society by providing means for designing affordable, flexible, and portable organic electronic devices. Their successful commercialization will depend on major scientific advancements, which will challenge human society to seek out ever more detailed and fundamental processes to command. Controlled polymerization affords such a power; allowing for the design of meticulous and precisely defined systems granting detailed insight into structure-property relationships in the polymer materials and bettering understanding of novel physical phenomena.

This dissertation primarily focuses on development and preparation of well-defined hierarchically organized macromolecular systems. The novel chain-growth polymerization methodologies …

Thioenamide Synthesis Inspired By Peptide Macrocycles, Joshua Allen Lutz

LSU Doctoral Dissertations

Despite advances in medicine, antibiotic resistance threatens to return once preventable diseases to the human population. The microbisporicins are 24-amino acid antibiotic peptides belonging to the lantibiotic class, which pathogens have been slow to develop resistance. The uncommon post-translational modification S-[(Z)-2-aminovinyl]-D-cysteine (AviCys) is likely crucial to their activity, and appears in a small number of other peptides with compelling biological activities. Total synthesis of an AviCys-containing peptide has eluded the chemical community.

The primary challenge of AviCys synthesis is the construction of a thioenamide functional group. We demonstrate that acid-promoted reactions between an amide and …

Turn-On Near-Infrared Fluorescent Sensors For Selective Monitoring Of Kinase Activity, Gerard Thomas Ducharme

LSU Doctoral Dissertations

Reliable and selective detection of specific biopolymers is critical in a broad range of biomedical and technological areas, including availability of simple and efficient point-of-care-compatible systems for the detection of prognostic, pharmacodynamic and predictive biomarkers. Monitoring epidermal growth factor receptor (EGFR) tyrosine kinase is of major significance due to its link to many epithelial cancers. This task is complicated by the high rate of mutation occurring in patients treated with kinase inhibitors. This dissertation describes a conceptually novel design and synthesis of turn-on near-infrared fluorescent sensors for selective and sensitive detection of EGFR. The fluorescent signal generation mechanism is based …

Chemosensors Based On Higher Energy Gap Control Of Fluorescence In Conjugated Polymers, Chun-Han Wang

LSU Doctoral Dissertations

Conjugated polymers (CPs) have been widely investigated for their remarkably high sensitivity towards various chemical detection applications. CPs can exhibit effective transduction of certain analyte binding events through changes in fluorescence. These changes include amplified fluorescence quenching ("turn-offmechanism") or an appearance of a fluorescent emission ("turn-onmechanism"). Whereas turn-offsensors can be readily designed and are widely used, amplifying turn-onsensors, from a practical standpoint, are more convenient to use but are more challenging to design.

This dissertation primarily focuses on the development and study of conjugated polymer based amplifying turn-onfluorescence chemosensors utilizing the novel “higher …

Photo-Induced Remote C-H Functionalization And New Thioglycoside Donor Development For O-Glycosylation, Shaofu Du

LSU Doctoral Dissertations

This dissertation focuses on the method development of C-H functionalization using photo-redox catalysis and the synthesis of new thioglycoside donors towards O-glycosylation. Chapter 1 describes the remote Csp³-H functionalization using photo-redox catalysis. The site-selective and high-yielding conversion of unreactive aliphatic C-H bonds has been a challenge for organic chemists for many years. In this work, inert C-H bonds were successfully converted to more useful C-C, C-N, and C-O bonds via hydrogen atom transfer (HAT), radical translocation and polar crossover. This mechanistic manifold was enacted by visible-light irradiation of o-diazoniaphenyl alkyl sulfones in the presence of Ru(bpy) …

Calculation Guided Rational Design And Synthesis Of Novel Cationic Fluorescent Meso–Pyridinium Bodipys For Bio-Imaging, Daniel J. Lamaster

LSU Doctoral Dissertations

Chapter 1 contains a brief overview of the history, synthesis, and properties of BODIPY dyes as well as that of the biomedical applications of bio-imaging and photodynamic therapy. Additionally, an overview of the theoretical framework of density functional theory and its time-dependent variant are provided. In Chapter 2, the effects of structural modification on the electronic structure and electron dynamics of cationic meso-(4-pyridyl)-BODIPYs were investigated. A library of 2,6-difunctionalized meso-(4-pyridyl)-BODIPYs bearing various electron-withdrawing substituents was designed and DFT calculations were used to model the redox properties, while TDDFT was used to determine the effects of functionalization on the excited …

Nmr Structural Investigation Of Chlamydial Protein Complex And Lysine Glycomimetic For Drug Design, Abigael Chebichiy Songok

LSU Doctoral Dissertations

Research and design of drugs for treatment against microbial infections require the study of pathogenic proteins involved during infection and replication. Drugs can be designed to interfere with the interaction network of these pathogenic proteins and inhibit the infection process. Determination of the structure and ligands of the target proteins in microbes is essential for designing mechanistic-based drugs. Two Chlamydia proteins involved in host cell invasion were investigated in this study. The goal is to identify amino acids involved at the binding interface of Chlamydia chaperon proteins Scc1 and Scc4 by solution NMR spectroscopy. This information will give a lead …

New Platinum(Ii) And Rhenium(I) Complexes Of "Linear" Chelate Ligands Terminated With Pyridyl Or Imidazolyl N-Donor Groups, Himali Kokila Ranasinghe Pilana Vithanage

LSU Doctoral Dissertations

The overall goal of this dissertation research is to design, synthesize, and study new Pt(II) and Re(I) complexes relevant to biomedical applications. One of the projects involves the assessment of the interactions of bulky tridentate carrier ligands with a bound guanine nucleobase derivative (G) in platinum complexes, with a goal of developing chemistry potentially relevant to active anti-cancer Pt drugs. In another project, the fac-[Re^I(CO)₃]⁺ core is used to prepare novel Re(I) complexes with the purpose of developing new linking chemistry relevant to ^99mTc and ¹⁸⁷Re radiopharmaceuticals. This research explores …

Higher Energy Gap Control Of Fluorescence In Conjugated Polymers, Chien-Hung Chiang

LSU Doctoral Dissertations

Chemo- and biosensors based on fluorescent conjugated polymer benefit from greater detection sensitivity due to amplification of the electronic perturbations produced by analyte binding. This amplification stems from the exciton-transporting properties of conjugated polymers. A conventional design paradigm relies on the analyte binding events which generate sites of lower energy relative to the polymer energy: either fluorescence quenching sites (turn-off sensors) or bathochromically shifted fluorophores (turn-on sensors). In both type sensors, the excitons migrate to the lower-energy site created by analyte binding.

This dissertation primarily focused the investigation of an alternative paradigm when analyte binding creates higher energy gap sites …

Synthesis And Characterization Of Covalent Adaptable Networks Comprised Of Dynamic Imine And Aminal Covalent Bonds, Albert Chao

LSU Doctoral Dissertations

The dissertation is about the design, synthesis and characterization of materials comprised of covalent adaptable networks (CANs). There are three chapters within this dissertation.

Chapter 1 contains a short overview of conventional thermosets and thermoplastics. A new strategy of combining advantages from thermosets and thermoplastics is utilizing dynamic covalent chemistry (DCC) for material design. Dynamic covalent bonds are able to undergo dynamic exchange which allow the material to adapt to a new state when under stimuli such as stress or strain. Material comprised of such reversible networks is called covalent adaptable networks (CANs). These types of reversible covalent bonds followed …

Development Of Remote Hydroxylation Via Redox Catalysis And Mild Activation Of Thioglycosides For O-Glycosylation, Kristina Deveaux

LSU Doctoral Dissertations

The focus of this dissertation is the development of a C-H functionalization method using redox catalysis and the synthesis of saccharides using thioglycosides. Chapter 1 is a review of C-H functionalization and visible-light photoredox catalysis. Over the years there have been many significant contributions to the field of C-H functionalization. Select examples have been discussed and a foundation for the method developed in chapter 2 has been outlined. Chapter 2 discusses the development and optimization of a C-H functionalization method. This approach uses the Tz^o directing group and Ir(ppy)₃ to activate a remote C-H bond via 1,6- and …

New Synthetic Reactions Towards Global Chlorination And Enamides Functionalization, Mirza Ardella Saputra

LSU Doctoral Dissertations

This dissertation focuses on two main projects, global chlorination and enamide functionalization, which both encompass in cationic intermediates. Inspired by the desires to find a new chlorination method, global chlorination project is emphasized in chapter one and chapter two, in which chapter one details various known chlorine-containing natural products, including alkyl chlorides and vinyl chlorides. This chapter also describes the previously known protocols to synthesize alkyl chlorides in the attempts of chlorosulfolipids total syntheses, as well as several known reactions to synthesize vinyl chlorides that are both important functional groups in organic synthesis. Chapter two depicts our novel synthetic reaction …