Organic Chemistry Commons^™

Monosaccharide Binding To Synthetic Carbohydrate Receptor Microarrays, Milan A. Shlain

Dissertations, Theses, and Capstone Projects

Chapter 1: A glycan detection platform comprised of synthetic carbohydrate receptors (SCRs) immobilized onto polymer brushes was prepared. SCR043, an alkene-containing SCR, was incorporated into grafted-from polymer brushes using hypersurface photolithography, resulting in microarrays of SCR043-functionalized polymer brushes, where brush height (h) and SCR grafting density (Γ) is controlled precisely at each feature in the array. The influence of h and Γ on the binding to five fluorescently labelled monosaccharides – α-glucose (α-Gluc-FL), α-galactose (α-Gal-FL), α-mannose (α-Man-FL), β-glucose (β-Gluc-FL), and β-galactose (β-Gal-FL) – in aqueous buffer …

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 …

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 …

Para-Methoxybenzylidene Acetal-Protected D-Glucosamine Derivatives As Ph-Responsive Gelators And Their Applications For Drug Delivery, Jonathan Bietsch, Logan Baker, Anna Duffney, Alice Mao, Mary Foutz, Cheandri Ackermann, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-based low molecular weight gelators (LMWGs) are compounds with the capability to self-assemble into complex molecular networks within a solvent, leading to solvent immobilization. This process of gel formation depends on noncovalent interactions, including Van der Waals, hydrogen bonding, and π–π stacking. Due to their potential applications in environmental remediation, drug delivery, and tissue engineering, these molecules have emerged as an important area of research. In particular, various 4,6-O-benzylidene acetal-protected D-glucosamine derivatives have shown promising gelation abilities. In this study, a series of C-2-carbamate derivatives containing a para-methoxy benzylidene acetal functional group were synthesized and characterized. These compounds exhibited good …

Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila

Dissertations

Organic synthesis has been significantly advanced with the employment of transition metal complexes. The discovery of transition metal catalysts provided the synthetic community with powerful tools for accelerating reactions and making them more selective and efficient. Many chemical reactions do not happen without a catalyst.

Iron-based catalysts have several advantages for the chemical industry because it is a non-toxic and ecologically friendly metal. Our group previously found that ferrocenium cations with a 3+ oxidation state of iron-catalyzed propargylic substitution reactions at low temperatures. The sandwich structure of ferrocenes allows substituents to be introduced on the cyclopentadienyl rings, which allows for …

Synthesis And Characterization Of 4,6-Protected Glucosamine Derivatives And Branched Glycoconjugates, Jonathan Bietsch

Chemistry & Biochemistry Theses & Dissertations

Low molecular weight gelators (LMWGs) are small molecules that self-assemble in appropriate solvents to form three dimensional networks that immobilize the solvent, creating a supramolecular gel. The self-assembly of LMWGs occurs through non-covalent interactions such as hydrogen bonding, aromatic interactions, donor-acceptor interactions, Van der Waals interactions, hydrophobic forces, halogen bonding, etc. Due to self-assembly occurring through reversible non-covalent interactions, supramolecular gels can undergo a gel to solution transformation. Because of this, these materials can be sensitive to external stimuli such as temperature changes, pH changes, and other stimuli that effect non-covalent interactions. This makes the synthesis of LMWG’s an appealing …

Stereocontrolled Mannosylation By Hydrogen-Bond-Mediated Aglycone Delivery, Catherine Alex

Dissertations

Stereocontrolled Mannosylation by Hydrogen-Bond-Mediated Aglycone Delivery

Carbohydrates are the essential bio-molecules of life as they form the forefront of interactions with receptors, proteins, pathogens, or neighboring cells. On cell-surfaces, carbohydrates are mostly found as linear or branched glycoconjugates, and a majority of them are linked via either 1,2-cis or 1,2-trans O-glycosidic linkages. There is no template-driven pathway for achieving the synthesis of glycans unlike other biomolecules like proteins and nucleic acids. The synthesis of 1,2-trans glycosides can be reliably achieved via the neighboring group assistance. The synthesis of 1,2-cis glycosides is difficult because, beyond weak anomeric effects, there are …

The Development Of Novel Carbohydrate-Based Gelators And Their Applications As Advanced Soft Materials, Joedian Morris

Chemistry & Biochemistry Theses & Dissertations

Low molecular weight gelators (LMWGs) are attractive molecules that have been explored extensively due to their practical applications in many disciplines. These small molecules self-assemble forming solid-like gels via three-dimensional cross-linked networks with the solvent as the key component within the matrix. Carbohydrate-based LMWGs are small molecules that can form solid-like gels in water, organic solvents, and aqueous solutions. They have great potential to be utilized in different applications because carbohydrates are biocompatible and can be made from easily accessible and renewable resources. Designing gelators is still a challenge within the field, even though researchers have developed tools to predict …

Synthesis Of Bulky And Polar Galactonoamidines For The Inhibition Of The Human Α-Galactosidase, Ifedi Orizu

Graduate Theses and Dissertations

Glycosidases are amongst the most abundant enzymes in nature. This is due to their role in the degradation of carbohydrates which are the major source of carbon or earth. The absence or malfunction of glycosidases is implicated in numerous diseases such as cancers, diabetes, and lysosomal storage disorders, which make them important drug targets for study in medicinal chemistry. The seminal work by Pauling and Wolfenden showed that enzymes bind to their substrate at the transition state with very strong affinity. Wolfenden estimated the dissociation constant to be around 10-22M. This encouraged the design of glycosidase inhibitors which mimicked one …

Synthesis Of Carbohydrate Based Macrolactones And Their Applications As Receptors For Ion Recognition And Catalysis, Surya B. Adhikari, Anji Chen, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Glycomacrolactones exhibit many interesting biological properties, and they are also important in molecular recognitions and for supramolecular chemistry. Therefore, it is important to be able to access glycomacrocycles with different sizes and functionality. A new series of carbohydrate-based macrocycles containing triazole and lactone moieties have been designed and synthesized. The synthesis features an intramolecular nucleophilic substitution reaction for the macrocyclization step. In this article, the effect of some common sulfonate leaving groups is evaluated for macrolactonization. Using tosylate gave good selectivity for monolactonization products with good yields. Fourteen different macrocycles have been synthesized and characterized, of which eleven macrocycles are …

Fine-Tuning Of Molecular Structures To Generate Carbohydrate Based Super Gelators And Their Applications For Drug Delivery And Dye Absorption, Jonathan Bietsch, Mary Olson, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-based low molecular weight gelators (LMWGs) exhibit many desirable properties making them useful in various fields including applications as drug delivery carriers. In order to further understand the structural connection to gelation properties, especially the influence of halide substitutions, we have designed and synthesized a series of para-chlorobenzylidene acetal protected D-glucosamine amide derivatives. Fifteen different amides were synthesized, and their self-assembling properties were assessed in multiple organic solvents, as well as mixtures of organic solvents with water. All derivatives were found to be gelators for at least one solvent and majority formed gels in multiple solvents at concentrations lower than …

Synthesis, Characterization, And Drug Delivery Applications Of Carbohydrate Based Low Molecular Weight Gelators, Kristen Elizabeth Bashaw

Chemistry & Biochemistry Theses & Dissertations

The main aim of the research focuses on the study of self-assembly and gelation by several classes of simple sugar derivatives and the potential applications of them as drug delivery vehicles. Since carbohydrates are naturally abundant renewable resources and are therefore readily available and many of them are inexpensive compared to other raw materials. They are also biocompatible which makes them suitable for a wide variety of applications. Combining the use of carbohydrates with low molecular weight gelators (LMWGs) we can introduce a new class of soft materials that are able to self-assemble into spheres, fibers, sheets, and micelles in …

Towards Completely Automated Glycan Synthesis, Matteo Panza

Dissertations

Carbohydrates are ubiquitous both in nature as biologically active compounds and in medicine as pharmaceuticals. Although there has been continued interest in the synthesis of carbohydrates, chemical methods require specialized knowledge and hence remain cumbersome. The need for development of rapid, efficient and operationally simple procedures has come to the fore. This dissertation focuses on the development of a fully automated platform that will enable both experts and non-specialists to perform the synthesis of glycans. Existing automated methods for the synthesis of oligosaccharides are highly sophisticated, operationally complex, and require significant user know-how. By contrast, high performance liquid chromatography (HPLC) …

Acid-Mediated N-Iodosuccinimide-Based Thioglycoside Activation For The Automated Solution-Phase Synthesis Of Α-1,2-Linked-Rhamnopyranosides, Victoria R. Kohout, Alyssa L. Pirinelli, Nicola L.B. Pohl

Chemistry Publications

Carbohydrate structures are often complex. Unfortunately, synthesis of the range of sugar combinations precludes the use of a single coupling protocol or set of reagents. Adapting known, reliable bench-chemistry reactions to work via automation will help forward the goal of synthesizing a broad range of glycans. Herein, the preparation of di- and tri-saccharides of alpha 1→2 rhamnan fragments is demonstrated using thioglycoside donors with the development for a solution-phase-based automation platform of commonly used activation conditions using N-iodosuccinimide (NIS) with trimethylsilyl triflate. Byproducts of the glycosylation reaction are shown to be compatible with hydrazine-based deprotection conditions, lending broader functionality …

Synthesis Of Neoglycoproteins/Neoglycopeptides And Their Immunological Evaluation In The Context Of Chagas Disease, Nathaniel Scott Schocker

Open Access Theses & Dissertations

The protozoan parasite, Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD), has a cell surface covered by immunogenic glycoconjugates. A synthetic glycoarray containing non-reducing α-galactopyranosyl moieties related to mucin O-glycans of the parasite T. cruzi was evaluated by a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) with sera from patients with chronic ChD, revealing the disaccharide Galα(1,3)Galβ as the immunodominant glycotope (Chapter 2). This disaccharide comprises the two terminal sugars of the known immunodominant glycotope Galα(1,3)Galβ(1,4)GlcNAcα, which is expressed on glycosylphosphatidylinositol-anchored mucins of the infective trypomastigote stage of T. cruzi and triggers high levels of protective anti-α-Gal antibodies (Abs) in infected …

Microarray Analysis As A Strategy To Identify And Characterize Glycome Regulatory, John F. Rakus

Chemistry Faculty Research

Glycosylation involves the post-translational addition of carbohydrates to protein molecules and is an intricate and indispensable biochemical process. Study of this complicated network of interactions is hindered by the lack of a coding template analogous to the genetic code, and by the vast structural complexity inherent to carbohydrate polymers. We use lectins (non-enzymatic carbohydrate-binding proteins of non-immunological origin) as microarray probes to identify carbohydrate features expressed on cellular surfaces. Specifically, we utilized lectin microarray technology to investigate the differences in carbohydrates expressed by the cell lines of the Nation Cancer Institute’s NCI-60 panel. Our investigation identified tissue-specific expression differences in …

Synthesis Of Novel Glycosylidene-Based Quinolines, Peter H. Dobbelaar

Seton Hall University Dissertations and Theses (ETDs)

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Synthesis And Evaluation Of Cyclopropanated Carbohydrates For Cns Disorders, Jaime Talisman

Seton Hall University Dissertations and Theses (ETDs)

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