Physical Sciences and Mathematics Commons^™

Synthesis Of Functionalized Tetrahydropyridine Derivatives Via Sncl4-Promoted [4+2] Cycloaddition Of Donor-Acceptor Cyclobutanes And Nitriles, David Tong

Electronic Thesis and Dissertation Repository

The formation of carbon-heteroatom bonds is pivotal in obtaining structural frameworks present in a variety of important natural products and bioactive molecules. In that regard, Lewis-acid promoted cycloadditions of strained carbocycles have proven to be powerful tools for the construction of heterocyclic frameworks. The Pagenkopf group was the first to discover the cycloaddition of donor-acceptor (DA) cyclopropanes with nitriles. Since the strain energy of cyclobutane is comparable to that of cyclopropane, our group has sought to extend to the comparatively unexplored homologous cyclobutane scaffold. Disclosed here is the first [4+2] cycloaddition of nitriles with DA cyclobutanes via Lewis-acid activation. This …

The Synthesis Of Heterocycles And Carbocycles And Work Towards Kainic Acid, Mathew L. Piotrowski

Electronic Thesis and Dissertation Repository

This thesis focuses on the synthesis of a variety of heterocycles and carbocycles such as pyrrolidines, dihydrofurans, dihydropyrroles, cyclopentenes, and 2,5-dihydrooxepines. Traditional synthetic methods are discussed first, followed by the manipulation of donor-acceptor cyclopropanes towards the above-mentioned compounds. This leads to a discussion about an important pyrrolidine-containing natural product known as kainic acid. Kainic acid has been studied in the neuroscience field for its biological properties which have led to a better understanding of common human neurological disorders like epilepsy, Huntington’s disease and the after-effects of strokes.

Chapter two focuses on a common rearrangement of donor-acceptor cyclopropanes known as the …

Functionalization Of Indoles And Donor-Acceptor Cyclopropanes And Their Application Towards The Total Synthesis Of Tronocarpine And Dippinine B, Lauren C. Irwin

Electronic Thesis and Dissertation Repository

The work disclosed in this dissertation outlines novel reactions involving indoles and their applications towards the total synthesis of natural products, tronocarpine and dippinine B.

Showcased in Chapter 2 is a novel mode of activation for donor-acceptor cyclopropanes via an external hydrogen bond. The hydrogen bond increases the cyclopropane’s electrophilicity permitting indole nucleophiles to open the ring. The result is 3-postion functionalized indoles.

An external hydrogen-bond donor, HFIP (1,1,1,3,3,3-hexafluoroisopropanol), is used as a solvent to provide the medium necessary for favourable hydrogen-bond interaction with donor-acceptor cyclopropanes. Hydrogen bond activation of donor-acceptor cyclopropanes was successful in generating a multitude of functional …

Methodologies For Metal Functionalization Of Phosphorus Based Photopolymer Networks, Vanessa Béland

Electronic Thesis and Dissertation Repository

Photopolymer networks with phosphonium cation, alkyl phosphine and olefin functionality were designed, synthesized and functionalized with metals by metathesis, coordination and hydrometallation reactions, respectively. The materials were strategically designed so that the metal functionalization step could be monitored and quantified. In some cases, this involved characterization by IR, NMR, or X-ray spectroscopic techniques, or by comparison to molecular analogues. It was found that by using a bi-functional photopolymer network, the material could be bi-metallized by orthogonal mechanisms. All metallized polymer networks were tested for their suitability as precursors to metal-containing ceramics. The polymers were pyrolyzed, and on analysis it was …

Strategies For The Preparation Of Functional Pendant Group Polymer Materials Via Click Chemistry, Rajeshwar Vasdev

Electronic Thesis and Dissertation Repository

This thesis describes the development of a polymer via a unique masking-unmasking strategy allowing for physical and chemical modification as desired. Modifiable polymers may lead to improved applications in drug delivery, photo-patterning and emissive materials design. In recent years, these potential traits have motivated the search for efficient protocols for the synthetic modification of polymers. Accordingly, click chemistry, characterized by fast, clean and high yielding reactions represents an effective tool for the modification of polymers. To achieve this goal, an efficient methodology is created to incorporate a highly reactive strained alkyne functional group as a modification site to expand the …

The Ghrelin Receptor And Its Appetite For Highly Potent Ghrelin Analogues, Tyler J. Lalonde

Electronic Thesis and Dissertation Repository

The growth hormone secretagogue receptor-1a (GHS-R1a) is expressed in many human tissues, most notably the hypothalamus, and causes an increase in appetite upon activation by its endogenous ligand, ghrelin. GHS-R1a is differentially expressed in malignant compared to benign tumours. Therefore, there is an interest in developing GHS-R1a-targeted peptides as novel drugs to modulate signaling for diseases such as cancer cachexia and obesity and to image the receptor for disease diagnosis and following progression.

Chapter 2 discusses a fluorescently labelled ghrelin analogue for imaging GHS-R1a in ex vivo biopsy analysis and in vivo distribution studies. The analogue was created through side-chain …

Synthesis And Characterization Of Peptide Nucleic Acids Incorporating Modified Nucleobases, Ali Heidari

Electronic Thesis and Dissertation Repository

Peptide Nucleic Acid (PNA), is a mimic of natural nucleic acids with exceptional binding properties. As such, numerous applications in biochemistry, medicine and biotechnology for PNA exist or have been proposed so far. Pseudo-complementary PNAs containing diaminopurine and thiouracil base pairs have been prepared and are shown to bind with high specificity and efficiency to complementary targets in double-stranded DNA by a mechanism termed ‘‘double duplex invasion’’ in which the duplex is unwound and both DNA strands are targeted simultaneously, each by one of the two pseudo-complementary PNAs. Chapter 2 describes a method for the preparation of modified nucleic acids …

Synthesis, Characterization, And Applications Of Group 13 And 14 Complexes Of Chelating Formazanate Ligands, Ryan R. Maar

Electronic Thesis and Dissertation Repository

This thesis describes the synthesis and characterization of group 13 (boron and aluminum) and group 14 (silicon, germanium, and tin) complexes supported by chelating formazanate [R¹-N-N=C(R³)-N=N-R⁵]^‒ ligands. The resulting complexes are redox-active and often luminescent. Chapters two to four describe the synthesis and characterization of boron formazanate adducts. The work in these chapters demonstrates that through structural modification of the formazanate ligand, solid-state- and NIR photoluminescence can be achieved. Furthermore, the formation of an oxoborane (B=O) afforded a highly photoluminescent formazanate adduct due to the structural rigidity imposed by the B=O bond. These …

Development Of Bioorthogonal Molecular Tools On Gold Nanoparticles, Wilson Luo

Electronic Thesis and Dissertation Repository

This thesis describes the development of bioorthogonal chemical tools — originally designed to form bonds cleanly and selectively in living systems — on gold nanoparticles (AuNPs) as a model reactive nanomaterial template to showcase chemical modifications in a facile and robust manner. To achieve this goal, new methodologies to cleanly incorporate strained alkyne (SA) and cargo-bearing triarylphosphine derivatives onto AuNPs were developed. The protocols described herein provide well-defined reactive AuNP interfaces that undergo bioorthogonal bond-forming and breaking reactions cleanly, selectively, and rapidly to enable chemical tuning of their properties and function.

In order to circumvent the high reactivity of SAs, …

Development Of In Situ Forming Hydrogels For Intra-Articular Drug Delivery, Andy Prince

Electronic Thesis and Dissertation Repository

Hydrogels are 3-dimensional crosslinked polymer networks that can absorb significant amounts of water. The physical properties associated with hydrogels affords them resemblance to biological tissues making them good candidates for biomedical applications. Many pharmaceuticals, specifically non-steroidal anti-inflammatory drugs (NSAIDs), have poor aqueous solubility, which limits their bioavailability and efficacy. People suffering from chronic osteoarthritis (OA) are required to frequently take large doses to mitigate pain, which can lead to serious side effects. Hydrogels are good strategies to deliver NSAIDs via articular injection because they can form solid gels in situ. This thesis describes the synthesis, formulation, mechanical testing, in …