Thesis (PH. D.)--Johns Hopkins University. / Biographical.

Thesis (Ph. D.)--Syracuse University, 2004. / "Publication number AAT 3132689."

Thesis (Ph. D.)--University of Wisconsin--Madison, 1975. / Vita. Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3805. Adviser: Scott K. Silverman. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

<p> N-acetyl neuraminic acid is most common member of the sialic acid family. This unique monosaccharide is displayed at the terminal position of oligosaccharides in glycoproteins and glycolipids on outer surface of a cell membrane. </p><p> The biological features of N-acetyl neuraminic acid involve cell-cell interactions in immunogenesis, as well as pathogens attacks, and overexpression in cancer cells. </p><p> The synthesis of sialic acid containing glycoconjugates is essential for a better understating of their biological function, as well as for the design of therapeutics. In addition, to the limitations of the enzymatic approach, chemical synthesis of these glycosidic linkages offer the opportunity to large scale isolation of common as well as uncommon oligosaccharides. </p><p> However, the stereocontrolled synthesis of sialic acid containing glycoconjugates is undoubtedly one of the most challenging research goals in the carbohydrate synthetic field. In particular, little is known on the effect of O-protecting groups in sialylation reactions. Recently we proved that a picoloyl group at C-4 can indeed favor an alpha sialylation if in the presence of an excess of triflic acid. Excellent stereoselectivities and yields were obtained with a wide range of galactosyl acceptors. </p><p> As a natural evolution of this finding, we decided to investigate the effect of picoloyl at other positions, as well stereoselectivities and yield in sialylations when di-picoloylated sialic acid donors are used. </p><p> Herein we report a systematic investigation of the regioselective introduction of picoloyl groups as well as the synthesis of a 7,8 di-picoloylated donor. The latter, when tested in sialylation reactions, gave exceptionally high yields and stereoselectivities.</p><p>

No description available.

<p> Current factories producing plant-based fossil-fuel replacements are neither environmentally friendly nor economically viable because their main product, bio-oil, is burned for heat rather than sold for profit. However, bio-oil is rich in potentially valuable aromatic compounds. In order to valorize bio-oil and improve the economic viability of the factories, we need to understand bio-oil&rsquo;s composition and the effect of processing parameters&mdash;such as plant feedstock and pretreatment method. Unfortunately, bio-oil is a complex lignocellulosic mixture that is difficult to analyze. To fully characterize the hundreds of compounds present, analysis typically requires top-end mass spectrometers and lengthy separations. This cost prohibits many laboratories from pursuing bio-oil research. Then time-consuming separations limit recursive analyses to optimize process parameters. The question takes shape: is it possible to analyze complex lignocellulosic mixtures without lengthy separations or top-end mass spectrometers? To assess the feasibility of rapid, affordable analysis, I set out to develop qualitative and quantitative methods using a quadrupole-time-of-flight (QTOF) mass spectrometer. I hypothesized that (a) ionization dopants could mitigate the need for lengthy separations pre-injection and that (b) tandem mass spectrometry could compensate for the midrange resolving power of the QTOF. To test this hypothesis, I started by analyzing another lignocellulosic biomaterial: autohydrolyzate, the product of hydrothermal pretreatment of biomass feedstocks. I observed that two anionic dopants&mdash;hydroxide and chloride&mdash;worked exceptionally well for selective analysis of the two major components of a lignocellulosic mixture, lignin- and carbohydrate-derivatives. Tandem mass spectrometry confirmed the game-changing selectivity of the dopants. With these favorable results, I applied the ionization dopants to two case studies. Chloride dopant and tandem mass spectrometry were employed to qualitatively analyze the little understood lignin-carbohydrate complexes found in lignocellulosic mixtures. Hydroxide dopant and tandem mass spectrometry were employed to quantitatively analyze the feasibility of valorizing biooil as a performance-enhancing diesel fuel additive. Both projects offered exciting success that redefined the scope of research possible using a QTOF. I demonstrated that by using ionization dopants and tandem mass spectrometry, it is possible for laboratories with limited means to use a cost-effective QTOF for both qualitative and quantitative analysis of complex lignocellulosic mixtures. </p><p>

<p> Molecular oxygen is an ideal source of oxygen atoms for synthetic transformations because it is inexpensive, abundant, and non-toxic. This dissertation presents the development of synthetic methods to oxidize alkenes to &alpha;-oxygenated ketones, hydroperoxides, alcohols, and endoperoxides using molecular oxygen under transition-metal or ambient-light catalysis. Chapter One describes a copper-catalyzed method to afford &alpha;-oxygenated ketones that can be further functionalized to give a variety of products. Chapter Two offers a light-catalyzed method for the synthesis of hydroperoxides from enol ethers and strained alkenes. Chapter Three discusses a cobalt-catalyzed synthesis of 1,2-dioxolanes and their applications in cancer biology. Chapter Four presents preliminary work in the construction of 1,2-dioxanes, which can be manipulated to furnish biologically active natural product derivatives.</p><p>

<p> Arginase is a manganese-containing enzyme that catalyzes the hydrolysis of L-arginine to yield L-ornithine and urea. It has been suggested that inhibition of arginase could be of therapeutic utility, and an arginase inhibitor is currently in phase I clinical trials for a variety of cancer subtypes. To date, the most promising inhibitors reported in the literature are &alpha;,&alpha;-disubstituted arginine analogs with a boronic acid warhead in place of the substrate guanidine group. However, the stereoselective approaches reported to date for this class of compounds have significant limitations and novel methods are needed. This research investigates two approaches: a route towards &alpha;,&alpha;-disubstituted amino acids via the enzyme-catalyzed desymmetrization of a meso diester and the utilization of the Petasis borono-Mannich reaction as an alternate enantioselective route for mono-substituted analogs.</p><p>

<p> Dysfunction of dopaminergic receptor signaling in the brain is a hallmark of a number of neurodegenerative pathologies. Of the five dopamine receptors, the D₃ subtype has emerged as a promising target for treating neurodegenerative diseases, especially Parkinson&rsquo;s disease, due to the specific distribution of this receptor in limbic and nigrostriatal brain regions known to be associated with motor functions. Not only have D₃-selective agonists shown positive effects in re-establishing control of motor activity in animals, but they also display neuroprotective activity and may be important in reducing the dyskinesia side-effect often seen with current non-selective dopaminergic therapies. Herein we report the extension of our previous studies of racemic 3-hydroxyphenyl pyrrolidines to their chiral analogues. We have used our best racemic D₃ ligand, <i>N</i>-nonyl-3-hydroxyphenyl pyrrolidine <b>74</b> (Ki = 13 nM), as starting point. Synthesis, characterization and D₃ receptor affinity of both the <i>R</i>- and <i> S</i>-enantiomer of <b>74</b> will be reported. In addition, we will describe SAR studies of new chiral <i>N</i>-functionalized-3-hydroxyphenylpyrrolidines (based upon the steric requirements of compound <b>74</b> in which the <i> N</i>-substituent has been designed to engage key residues in the secondary binding site of the D₃ receptor to enhance affinity and selectivity. </p><p>