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Title: Methodologies Towards One Pot Synthesis of α-Arylated Amino Esters And Applications in Total Synthesis.
Creator: Samanta, Shyam S., Roche, Stephane P., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: In this dissertation, we discuss the development of a synthetic method to functionalize various α-haloglycine esters, as key precursors to a large variety of non-proteinogenic α-amino acids (Xaas). At first, we discovered a very practical and high yielding acetyl chloride-mediated cascade reaction to synthesize α-arylated amino esters in one-pot. In this multicomponent reaction (MCR), a primary carbamate was condensed with a glyoxylate, followed by an in situ halogenation which proved...
Show moreIn this dissertation, we discuss the development of a synthetic method to functionalize various α-haloglycine esters, as key precursors to a large variety of non-proteinogenic α-amino acids (Xaas). At first, we discovered a very practical and high yielding acetyl chloride-mediated cascade reaction to synthesize α-arylated amino esters in one-pot. In this multicomponent reaction (MCR), a primary carbamate was condensed with a glyoxylate, followed by an in situ halogenation which proved essential to trigger the final Friedel−Crafts functionalization. After careful reaction optimization, a plethora of arene nucleophiles were reacted with high regioselectively in CHCl3 at low temperatures (Method A) while less activated arenes reacted more cleanly in CH3CN and at higher temperatures (Method B). To broaden the scope of this reaction to acid sensitive nucleophiles, a one-pot reaction was designed via evaporation of all acid by-products at the α-haloglycine stage. The anion-binding Schreiner’s thiourea catalyst proved to be extremely efficient to promote this complementary approach (Method C) which relies on the chloride leaving group activation by the catalyst to assist the functionalization stage and deliver the α-amino ester product. In the second chapter, some highly practical and efficient preparations of α-haloglycine esters in one-pot have been developed to generate useful precursors of non-proteinogenic α-amino esters. Also, a mild and unique AcOH(cat.)/AcCl system was found to promote an autocatalytic-like condensation/deoxy halogenation and facilitate the multicomponent assembly of non-proteinogenic α-amino esters. Friedel–Crafts reaction between α-chloroglycine and N-methylindole have been studied in details to understand the mechanistic intricacy of this reaction. Our findings through the initial kinetic profiling support that the arylation likely proceeds via a SN1-like (or SN2C+) mechanism. In third chapter, we discuss the development of the most challenging α,α-disubstituted amino esters in a multicomponent fashion. Our results highlight that the MCR proceeds via the formation of an enamide intermediate, which is further tautomerized to corresponding iminium to produce the desired product. In collaboration with Eli Lilly at the Automated Synthesis Laboratory (ASL), we have developed silver (I) salts mediated Friedel–Crafts reaction for synthesis of α-trifluoromethylated α-amino esters on a fully automatized robot.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013160
Subject Headings: Esters, Synthesis, Amino Acids
Format: Document (PDF)

Title: I. Synthesis and spectroscopic characterization of poly(bis(cyclopentadienyl)titanium(IV) squarate);. II. Reaction of the tetrachloroplatinate (II) ion with the basic trifunctional amino acids.
Creator: Williams, Melanie MacDonald, Florida Atlantic University
Abstract/Description: Reaction of Cp2TiCl2 with the dianion of squaric acid yields a polymer in which the squarate ion is present as a simple bidentate ligand with two uncoordinated carbonyl groups. The polymeric structure was established using light scattering photometry and geometric arguments. The structure and bonding of the polymer was confirmed using infrared, Raman, and 1H-NMR spectroscopy, and mass spectrometry. The 1H-NMR spectrum of the polymer shows two complex multiplets for the cyclopentadienyl rings,...
Show moreReaction of Cp2TiCl2 with the dianion of squaric acid yields a polymer in which the squarate ion is present as a simple bidentate ligand with two uncoordinated carbonyl groups. The polymeric structure was established using light scattering photometry and geometric arguments. The structure and bonding of the polymer was confirmed using infrared, Raman, and 1H-NMR spectroscopy, and mass spectrometry. The 1H-NMR spectrum of the polymer shows two complex multiplets for the cyclopentadienyl rings, and indicates inhibition of rotation of the Cp rings. Reaction of the tetrachloroplatinate ion with lysine, arginine, and histidine, using 1:1 ligand to metal ratios was investigated. The amino acids used were in the cationic, anionic and zwitterionic forms. The structures of the products obtained were investigated using infrared spectroscopy, light scattering photometry, 1H-NMR spectroscopy and mass spectrometry. Preliminary biological studies were conducted on the histidine products.
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Date Issued: 1989
PURL: http://purl.flvc.org/fcla/dt/14553
Subject Headings: Organotitanium compounds, Amino acids
Format: Document (PDF)

Title: Are free amino acids responsible for the “host factor” effects on symbiotic zooxanthellae in extracts of host tissue?.
Creator: Cook, Clayton B.
Date Issued: 2001
PURL: http://purl.flvc.org/FCLA/DT/2783225
Subject Headings: Dinoflagellates --Physiology, Amino acids, Zooxanthella, Marine biology
Format: Document (PDF)

Title: Biosynthetic Studies of the Alkaloid, Stevensine, in a Cell Culture of the Marine Sponge Teichaxinella morchella.
Creator: Andrade, Paul, Willoughby, Robin, Pomponi, Shirley A., Kerr, Russell G.
Date Issued: 1999
PURL: http://purl.flvc.org/FCLA/DT/3158768
Subject Headings: Alkaloids, Sponges, Marine invertebrates, Amino acids, Biosynthetic Pathways
Format: Document (PDF)

Title: Gapless alignment revisited.
Creator: Raley, Elizabeth Anne, Florida Atlantic University, Yu, Yi-Kuo
Abstract/Description: The purpose of sequence alignment is to detect mutual similarity, characterized by the so-called "alignment score", between sequences compared. To quantitatively assess the confidence level of an alignment result requires the knowledge of alignment score statistics under a certain null model and is the central issue in sequence alignment. In this thesis, the score statistics of Markov null model were revisited and the score statistics of non-Markov null model were investigated for two state...
Show moreThe purpose of sequence alignment is to detect mutual similarity, characterized by the so-called "alignment score", between sequences compared. To quantitatively assess the confidence level of an alignment result requires the knowledge of alignment score statistics under a certain null model and is the central issue in sequence alignment. In this thesis, the score statistics of Markov null model were revisited and the score statistics of non-Markov null model were investigated for two state-of-the-art algorithms, namely, the gapless Smith-Waterman and Hybrid algorithms. These two algorithms were further used to find highly related signals in unrelated sequences and in weakly related sequences corresponding, respectively, to Markov null model and non-Markov null model. The confidence levels of these models were also studied. Since the sequence similarity we are interested in comes from evolutionary history, we also investigated the relationship between sequence alignment, the tool to find similarity, and evolution. The average evolution distance between the daughter sequences was found and compared with their expected values, for individual trees and as an average over many trees.
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Date Issued: 2001
PURL: http://purl.flvc.org/fcla/dt/12856
Subject Headings: Bioinformatics, Amino acid sequence--Databases, Markov processes
Format: Document (PDF)

Title: CELLULAR REQUIREMENTS FOR MBLAC1 EXPRESSION AS ASSESSED IN MBLAC1-/- MOUSE EMBRYONIC FIBROBLASTS.
Creator: McGovern, Samantha, Blakely, Randy, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Science
Abstract/Description: The majority of research on drug addiction centers on dopamine (DA)- driven synaptic plasticities and how these changes ultimately lead to compulsive drug seeking. However, growing evidence supports a role of glial factors in various steps that lead to drug abuse and addiction. In this regard, significant evidence implicates glial glutamate (Glu) transporters (GLT-1) and cystine/Glu exchangers (xCT) in determining synaptic and extrasynaptic levels of Glu that support the acute and chronic...
Show moreThe majority of research on drug addiction centers on dopamine (DA)- driven synaptic plasticities and how these changes ultimately lead to compulsive drug seeking. However, growing evidence supports a role of glial factors in various steps that lead to drug abuse and addiction. In this regard, significant evidence implicates glial glutamate (Glu) transporters (GLT-1) and cystine/Glu exchangers (xCT) in determining synaptic and extrasynaptic levels of Glu that support the acute and chronic actions of drugs of abuse. -lactam antibiotics have been found in rodent models to upregulate CNS GLT-1 and xCT and thereby contribute to reinstatement after chronic drug exposure and withdrawal. Previously, the Blakely lab identified a glial expressing gene, swip-10, in Caenorhabditis elegans, whose deletion results in the hyperdominergic phenotype Swimming-Induced Paralysis (Swip), supported by Glu signalingdependent DA neuron hyperexcitability that ultimately drives oxidative stress and DA neuron degeneration. Both SWIP-10 and its putative mammalian ortholog MBLAC1 possess a highly conserved metallo -lactamase domain, and MBLAC1 has been found to bind the Glu modulating, b-lactam antibiotic ceftriaxone (Cef). Indeed, immunodepletion studies indicate that MBLAC1 may be the major highaffinity Cef-binding protein in the brain, leading to the hypothesis that MBLAC1 has a Glu modulatory role(s). Recently a functional role of MBLAC1 been proposed, involving activity as a 3’ exonuclease that processes polyA- mRNAs, including RNAs encoding cell replication-dependent histones. How this role, or others, may support the actions of MBLAC1 in the brain and the non-microbial actions of Cef to extracellular Glu homeostasis, is unclear. Recently, the Blakely lab generated Mblac1-/- mice as a tool to investigate these issues. The following work investigated the requirements of MBLAC1 in growth and the actions of Cef in mouse embryonic fibroblasts (MEFs) cultured from either Mblac1+/+ and Mblac1-/- mice. The presented data suggested that Mblac1-/- MEFs display attenuated growth and cell proliferation relative to Mblac1+/+ MEFs. For the first time, the in vitro protective actions of Cef against oxidative stress is shown to be dependent on MBLAC1. The following studies presented contribute to a definition of the role of MBLAC1 and as a Cef binding protein in native preparations, with findings that can drive models for the role of MBLAC1 in the CNS.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013395
Subject Headings: Drug addiction--Research, Amino Acid Transport System X-AG, Mice, Fibroblasts
Format: Document (PDF)

Title: Reciprocal regulation between taurine and glutamate response via Ca2+ - dependent pathways in retinal third-order neurons.
Creator: Bulley, Simon, Shen, Wen
Date Issued: 2010-08-24
PURL: http://purl.flvc.org/fcla/dt/3327274
Subject Headings: Amacrine Cells*/cytology, Amacrine Cells*/drug effects, Amacrine Cells*/metabolism, Ambystoma, Calcium/metabolism, Calcium Channels/metabolism, Cells, Cultured, Enzyme Inhibitors/metabolism, Excitatory Amino Acid Agonists/pharmacology, GABA Antagonists/pharmacology, Glutamic Acid/metabolism, Glycine Agents/pharmacology, Kainic Acid/pharmacology, Membrane Glycoproteins, Membrane Potentials, Neurotransmitter Agents, Retinal Ganglion Cells, Signal Transduction, Synaptic Transmission
Format: Document (PDF)

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