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- Title
- 2012-2013 Program Review Chemistry.
- Creator
- Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Florida Atlantic University Departmental Dashboard Indicators. Department program reviews for Charles E. Schmidt College of Science, Florida Atlantic University.
- Date Issued
- 2012-2013
- PURL
- http://purl.flvc.org/fau/fd/FA00007687
- Format
- Document (PDF)
- Title
- 2010-2011 Program Review Chemistry.
- Creator
- Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Florida Atlantic University Departmental Dashboard Indicators. Department program reviews for Charles E. Schmidt College of Science, Florida Atlantic University.
- Date Issued
- 2010-2011
- PURL
- http://purl.flvc.org/fau/fd/FA00007680
- Format
- Document (PDF)
- Title
- 2013-2014 Program Review Chemistry.
- Creator
- Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Florida Atlantic University Departmental Dashboard Indicators. Department program reviews for Charles E. Schmidt College of Science, Florida Atlantic University.
- Date Issued
- 2013-2014
- PURL
- http://purl.flvc.org/fau/fd/FA00007694
- Format
- Document (PDF)
- Title
- 2016-2017 Program Review Chemistry.
- Creator
- Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Florida Atlantic University Departmental Dashboard Indicators. Department program reviews for Charles E. Schmidt College of Science, Florida Atlantic University.
- Date Issued
- 2016-2017
- PURL
- http://purl.flvc.org/fau/fd/FA00007715
- Format
- Document (PDF)
- Title
- 2009-2010 Program Review Chemistry.
- Creator
- Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Florida Atlantic University Departmental Dashboard Indicators. Department program reviews for Charles E. Schmidt College of Science, Florida Atlantic University.
- Date Issued
- 2009-2010
- PURL
- http://purl.flvc.org/fau/fd/FA00007673
- Format
- Document (PDF)
- Title
- 2015-2016 Program Review Chemistry.
- Creator
- Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Florida Atlantic University Departmental Dashboard Indicators. Department program reviews for Charles E. Schmidt College of Science, Florida Atlantic University.
- Date Issued
- 2015-2016
- PURL
- http://purl.flvc.org/fau/fd/FA00007708
- Format
- Document (PDF)
- Title
- 2014-2015 Program Review Chemistry.
- Creator
- Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Florida Atlantic University Departmental Dashboard Indicators. Department program reviews for Charles E. Schmidt College of Science, Florida Atlantic University.
- Date Issued
- 2014-2015
- PURL
- http://purl.flvc.org/fau/fd/FA00007701
- Format
- Document (PDF)
- Title
- Aggregation kinetics of A\U+fffd\ peptides and the inhibition effects of small molecules on A\U+fffd\ peptide aggregation.
- Creator
- Hijazi, Ahmad Alex., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The pathology of Alzheimer's disease (AD) remains elusive. Competing evidence links amylois \U+fffd\-peptide (A\U+fffd\) amyloid formation to the phenotype of AD (1). The mechanism of amyloid fibril formation has been an ongoing investigation for many years. A\U+fffd\10-23 peptide, a fragment of A\U+fffd\1-42 peptide, contained crucial hydrophobic core residues (2). In this study, an investigation was launched to study the aggreagation process of A\U+fffd\1023 peptide and its ability to form...
Show moreThe pathology of Alzheimer's disease (AD) remains elusive. Competing evidence links amylois \U+fffd\-peptide (A\U+fffd\) amyloid formation to the phenotype of AD (1). The mechanism of amyloid fibril formation has been an ongoing investigation for many years. A\U+fffd\10-23 peptide, a fragment of A\U+fffd\1-42 peptide, contained crucial hydrophobic core residues (2). In this study, an investigation was launched to study the aggreagation process of A\U+fffd\1023 peptide and its ability to form amyloid fibrils. Furthermore, the presence of its hydrophobic core showed importance for its ability to aggregate and form amyloid fibrils. Thereafter, the inhibition of A\U+fffd\1-42 peptide aggregation was studied by using pyrimidine-based compounds. A\U+fffd\1-42 peptides, known to be neurotoxic, aggregate to form amyloid fibrils (3). This investigation may provide insight into the development of novel small molecular candidates to treat AD.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3358550
- Subject Headings
- Amyloid beta-protein, Proteins, Metabolism, Disorders, Prions, Alzheimer's disease
- Format
- Document (PDF)
- Title
- A New Approach to Sensitized Luminescence in Trivalent Lanthanide Coordination Polymers: From Fundamental Luminescence and Crystal Engineering Toward Sensing Applications.
- Creator
- Einkauf, Jeffrey D., De Lill, Daniel T., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Luminescent lanthanide containing coordination polymers and metal-organic frameworks hold great potential in many applications due to their distinctive spectroscopic properties. While the ability to design coordination polymers for specific functions is often mentioned as a major benefit bestowed upon these compounds, the lack of a meaningful understanding of the crystal engineering and luminescence in lanthanide coordination polymers remains a significant challenge toward functional design....
Show moreLuminescent lanthanide containing coordination polymers and metal-organic frameworks hold great potential in many applications due to their distinctive spectroscopic properties. While the ability to design coordination polymers for specific functions is often mentioned as a major benefit bestowed upon these compounds, the lack of a meaningful understanding of the crystal engineering and luminescence in lanthanide coordination polymers remains a significant challenge toward functional design. Currently, the study of luminescence attributed to these compounds is based on the antenna effect as derived from molecular systems, where organic antennae are used to facilitate lanthanide-centered luminescence. This molecular based approach does not take into account the unique features of extended network solids, particularly the formation of band structure. By comparing molecular and band-based approaches, it was determined that the band structure of the organic sensitizing linker needs to be considered when evaluating the luminescence of lanthanide coordination polymers. This new model, as well as work on the crystal engineering and sensor applications of these materials will be presented.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004890, http://purl.flvc.org/fau/fd/FA00004890
- Subject Headings
- Rare earth metals., Lanthanide shift reagents., Organic compounds--Synthesis., Inorganic compounds--Synthesis., Metallic composites--Speciation., Polymeric composites., Organorare earth metal compounds., Nanostructured materials.
- Format
- Document (PDF)
- Title
- A STUDY ON THE CLINICAL RELEVANCE OF METALLOPROTEINASE INHIBITION.
- Creator
- Onwuha-Ekpete, Lillian, Fields, Gregg, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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The Metzincins are a superfamily of zinc-dependent endopeptidases associated with the regulation of the extracellular matrix (ECM). Their members include A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs), A Disintegrin and Metalloproteinases (ADAMs), and the matrix metalloproteinases (MMPs). Metzincins exhibit diverse functions associated with both physiological and pathological states that include the proteolytic degradation of the ECM, regulation of various growth...
Show moreThe Metzincins are a superfamily of zinc-dependent endopeptidases associated with the regulation of the extracellular matrix (ECM). Their members include A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs), A Disintegrin and Metalloproteinases (ADAMs), and the matrix metalloproteinases (MMPs). Metzincins exhibit diverse functions associated with both physiological and pathological states that include the proteolytic degradation of the ECM, regulation of various growth factors, cell surface receptors, and chemokines, and mediation of biological functions such as extravasation, survival, and proliferation. In pathological conditions such as cancer associated with chronic inflammation and multiple sclerosis associated with neurodegeneration, dysregulation of Metzincin activities are a hallmark of disease progression and severity. Hence, Metzincins are therapeutic targets for various disease states and research into optimal Metzincin inhibitor design is an ongoing exploit.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013615
- Subject Headings
- Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, T cells, Immunology
- Format
- Document (PDF)
- Title
- Synthesis and structural characterization of intermediates towards the preparation of a polyphosphonate ester containing L-dopa for the potential treatment of Parkinson's disease.
- Creator
- Chamely-Wiik, Donna M., Florida Atlantic University, Haky, Jerome E., Carraher, Charles E., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
We have synthesized intermediates towards the preparation of a polyphosphonate ester containing L-dopa for the potential treatment of Parkinson's disease. A synthetic strategy was devised to be more reproducible than the original strategy. We discovered some very interesting chemistry of one of the intermediates produced from this new scheme. We synthesized L-N-(butyloxycarbonyl)-3-(3-hydroxy-ethyl-4-(benzyloxy)-phenyl)alanine benzylester, a compound containing a secondary alcohol moiety that...
Show moreWe have synthesized intermediates towards the preparation of a polyphosphonate ester containing L-dopa for the potential treatment of Parkinson's disease. A synthetic strategy was devised to be more reproducible than the original strategy. We discovered some very interesting chemistry of one of the intermediates produced from this new scheme. We synthesized L-N-(butyloxycarbonyl)-3-(3-hydroxy-ethyl-4-(benzyloxy)-phenyl)alanine benzylester, a compound containing a secondary alcohol moiety that had a unique set of characteristics. Upon reduction of the N-(tert-butyloxycarbonyl)-3-(3-acetyl-4-benzyloxyphenyl)-L-alanine benzylester, which contained a ketone moiety, to produce the secondary alcohol, we discovered that the materials that were formed included a pair of diastereomers of the secondary alcohol, each diastereomer also exhibiting two individually stable conformational isomers. We believe that the conformational isomers were generated by rotation of the C-N bond of the BOC carbamate, and were so stable that they could be separated by HPLC and NMR techniques. Energy optimization studies and molecular modeling techniques were performed using HyperChem, and rotational barrier energy values were calculated for the different conformational isomers for each of the diastereomers. HPLC and NMR techniques were also used to obtain information about these materials. Using the calculated data from these studies, and analyzing the HPLC chromatograms and NMR spectra we were able to fully determine the assignments for the diastereomers and the individual conformational isomers. We discovered that the SS form was synthesized preferentially over the SR form and that in both cases the E conformation was energetically more stable than the Z form. Octanol/water partition coefficient values (Log P0ct) were also determined and compared to L-dopa and dopamine. We concluded that the values for the dimeric compound that we synthesized and many of its potential products of degradation were significantly higher than that for both L-dopa and dopamine. This may be an indication that this material has a higher degree of lipophilicity than L-dopa itself, having more potential to cross the blood brain barrier. We believe that these intermediate materials serve as good indication of how a polyphosphonate ester containing L-dopa would compare as a potential drug for Parkinson's disease.
Show less - Date Issued
- 2004
- PURL
- http://purl.flvc.org/fcla/dt/12108
- Subject Headings
- Parkinson's disease--Treatment, Antiparkinsonian agents, Dopa, Organophosphorus compounds--Synthesis, Chemistry, Analytic
- Format
- Document (PDF)
- Title
- ALLENYL ESTER BUILDING BLOCKS: THEIR APPLICATION TO THE SYNTHESIS OF BRIDGED BICYCLIC COMPOUNDS AND UTILITY AS PRENUCLEOPHILES IN THE DIASTEREOSELECTIVE FORMATION OF ALL-CARBON QUATERNARY ALDOL PRODUCTS.
- Creator
- Maki, Samantha, Lepore, Salvatore, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
The present dissertation will be largely focused on the synthesis of various [3.2.1] bridged bicycles using allenyl esters. Chapter one will present the importance of various [3.n.1] bridged bicycles in medicinal chemistry. A three-step synthetic route will then be described on how to produce a small library of [3.n.1] bridged bicycles using allenyl esters in an annulation reaction. The [3.n.1] bicyclic diketones can then undergo Grob fragmentation to deliver highly functionalized medium...
Show moreThe present dissertation will be largely focused on the synthesis of various [3.2.1] bridged bicycles using allenyl esters. Chapter one will present the importance of various [3.n.1] bridged bicycles in medicinal chemistry. A three-step synthetic route will then be described on how to produce a small library of [3.n.1] bridged bicycles using allenyl esters in an annulation reaction. The [3.n.1] bicyclic diketones can then undergo Grob fragmentation to deliver highly functionalized medium sized rings. Studies towards the total synthesis of vitisinol D, a highly functionalized [3.2.1] bridged bicycle will be discussed. In chapter two, synthesis knowledge gleamed from chapter one will be used to create a model route to form simplified versions of vitisinol D, called resveramorphs. These resveramorphs are structurally similar to resveratrol but possess rigid three-dimensional configuration desired in drug design. The synthetic route to create a variety of resveramorphs will be reported. The sub-nanomolar results of various resveramorph compounds in a Drosophila melanogaster neural tissue model under oxidative stress will be reported. Chapter three will focus on the use of allenyl esters as prenucleophiles to produce triply diastereoselective β-hydroxy esters containing all carbon α-quaternary centers. The challenges in the opitmization of this novel reaction will be described. The relative stereochemistry of the β-hydroxy ester products will be presented using various techniques including X-ray crystallography, 1D NMR, 2D NMR, and force field calculations (MM2). A closed transition state mechanism will be proposed to describe the diastereoselectivity that is observed in the reaction. Additionally, a short indanone synthesis will be shown as a potential application for this novel reaction.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013391
- Subject Headings
- Bicyclic compounds, Esters, Diastereoisomers
- Format
- Document (PDF)
- Title
- Characterization of Disulfide Constrained Natural Peptides.
- Creator
- Hoggard, Mickelene F., Cudic, Mare, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The use of peptide drugs has gained popularity recently. Peptides are attractive drug targets due to their high specificity and potency towards their biological targets. A drawback for peptide drugs is a lack of stability for oral delivery. Two classes of disulfide-rich peptides, conotoxins and cyclotides, have been shown to have higher stability than linear peptides thanks to their disulfide connectivity. Conotoxins are present in the venom of cone snails, a carnivorous marine mollusk that...
Show moreThe use of peptide drugs has gained popularity recently. Peptides are attractive drug targets due to their high specificity and potency towards their biological targets. A drawback for peptide drugs is a lack of stability for oral delivery. Two classes of disulfide-rich peptides, conotoxins and cyclotides, have been shown to have higher stability than linear peptides thanks to their disulfide connectivity. Conotoxins are present in the venom of cone snails, a carnivorous marine mollusk that preys upon fish, worms, or other mollusks. Conotoxins are promising drugs leads with great prospects in the treatment of diseases and disorders such as chronic pain, multiple sclerosis and Parkinson’s and Alzheimer’s diseases. Cyclotides, which are cyclic cysteine knot containing peptides, isolated from the Violaceae (violet), Rubiaceae (coffee), and Cucurbitaceae (cucurbit) families and they have a wide range of biological activities, such as anti-HIV, uterotonic, and antimicrobial. P-superfamily framework IX conotoxins (C-C- C-CXC- C) contain the same cysteine framework, homologous sequences, and similar 3D structures to cyclotides. The knot containing conotoxins have been identified in several Conus species, but this work focuses on those from Conus brunneus, Conus purpurascens, and Conus gloriamaris. The cysteine knot motif of cyclotides and P-superfamily conotoxins is characterized by a cyclic backbone and six-conserved cysteine residues that form the three-disulfide bridges of the “knot”. This motif provides cyclotides and conotoxins with superior stability against thermal, chemical, and enzymatic degradation; marking them as potential frameworks for peptide drug delivery. Presented are details on the isolation of conotoxins and cyclotides, from Viola tricolor, and the characterization of their activity in the well-characterized Drosophila melanogaster giant fiber system (GFS) neuronal circuit, which contains GAP, acetylcholine, and glutamate synapses. The transcriptomes of two Conus brunneus specimens were assembled and mined for P-superfamily framework IX conotoxins. Eleven mature P-superfamily framework IX conotoxins were identified in the crude venom.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00005955
- Subject Headings
- Peptide drugs, Cyclotides, Conotoxins
- Format
- Document (PDF)
- Title
- Chemical Studies of Caribbean Marine Organisms.
- Creator
- Vansach, Tifanie, West, Lyndon M., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The projects described in this dissertation concentrated on investigating Caribbean species for qualitative and quantitative chemical differences. Chapter one includes a brief update on the status of natural products as drugs, a discussion of the biodiversity of Caribbean marine organisms as well as a discussion about the chemistry of algae and sponges. In chapter two, an experiment to test for possible effects of warmer, more acidic water and how that will impact coral reef organisms was...
Show moreThe projects described in this dissertation concentrated on investigating Caribbean species for qualitative and quantitative chemical differences. Chapter one includes a brief update on the status of natural products as drugs, a discussion of the biodiversity of Caribbean marine organisms as well as a discussion about the chemistry of algae and sponges. In chapter two, an experiment to test for possible effects of warmer, more acidic water and how that will impact coral reef organisms was conducted. Six common Caribbean coral reef sponge species were grown in seawater for 24 days ranging from values experienced at summer-maxima (temperature = 28 ºC; pH = 8.1) to those predicted for the year 2100 (T = 31 ºC; pH = 7.8). For each species, attachment rates, growth, and survival were similar between temperature and pH levels. Only two metabolite concentrations varied significantly between treatments but were similar to baseline levels. In chapter three, a chemical survey of Florida Keys algae was performed using MeOH extraction and HP-20 SPE with varying Me2CO:H2O solutions. 1H NMR spectra were collected for each fraction and analyzed for interesting signals. A Laurencia sp. was extracted and found to contain the known compound isodactylyne (61) with the structure determined using spectroscopic analyses. In chapter four, a Laurencia obtusa specimen was investigated to determine the compound causing oxygenated signals between 4.50 – 4.80 ppm in the 1H NMR spectra observed in chapter three. A large scale extraction and fractionation was performed and the compound was determined to be 1-O-palmitoyl-2-O-myristoyl-3-O-(6-sulfo-α- D-quinovo-pyranosyl)-glycerol (63). In chapter five, the isolation and structural elucidation of a new compound, furocaespitanenone (64) and two known compounds (10R)- and (10S)-10-O-methylfurocaespitanelactol 65 and 66, from a Laurencia sp. collected off of the Florida Keys using MeOH extraction and HP-20 column chromatography is described. A potential biosynthesis of 64 from furocaepsitane (68) is proposed.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013274
- Subject Headings
- Marine organisms, Caribbean, Algae--chemistry, Sponges--Caribbean Sea, Chemistry
- Format
- Document (PDF)
- Title
- Cell-surface glycan-lectin interactions for biomedical applications.
- Creator
- Rodriguez Benavente, Maria Carolina, Lepore, Salvatore D., Cudic, Predrag, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Carbohydrate recognition is one of the most sophisticated recognition processes in biological systems, mediating many important aspects of cell-cell recognition, such as inflammation, cell differentiation, and metastasis. Consequently, lectin-glycan interactions have been intensively studied in order to mimic their actions for potential bioanalytical and biomedical applications. Galectins, a class of ß-galactoside-specific animal lectins, have been strongly implicated in inflammation and...
Show moreCarbohydrate recognition is one of the most sophisticated recognition processes in biological systems, mediating many important aspects of cell-cell recognition, such as inflammation, cell differentiation, and metastasis. Consequently, lectin-glycan interactions have been intensively studied in order to mimic their actions for potential bioanalytical and biomedical applications. Galectins, a class of ß-galactoside-specific animal lectins, have been strongly implicated in inflammation and cancer. Galectin-3 is involved in carbohydrate-mediated metastatic cell heterotypic and homotypic adhesion via interaction with Thomsen-Friedenreich (TF) antigen on cancer-associated MUC1. However, the precise mechanism by which galectin-3 recognizes TF antigen is poorly understood. Our thermodynamic studies have shown that the presentation of the carbohydrate ligand by MUC1-based peptide scaffolds can have a major impact on recognition, and may facilitate the design of more potent and specific galectin-3 inhibitors that can be used as novel chemical tools in dissecting the precise role of galectin-3 in cancer and inflammatory diseases. Another lectin, odorranalectin (OL), has been recently identified from Odorrana grahami skin secretions as the smallest cyclic peptide lectin, has a particular selectivity for L-fucose and very low toxicity and immunogenicity, rendering OL an excellent candidate for drug delivery to targeted sites, such as: (1) tumor-associated fucosylated antigens implicated in the pathogenesis of several cancers, for overcoming the nonspecificity of most anticancer agents; (2) the olfactory epithelium of nasal mucosa for enhanced delivery of peptide-based drugs to the brain.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00004405
- Subject Headings
- Biopharmaceutics, Carbohydrates -- Therapeutic use, Cell differentiation, Drug delivery systems, Glycoproteins, Glycoslation, Mice as laboratory animals, Peptides -- Derivatives, Pharmaceutical biotechnology
- Format
- Document (PDF)
- Title
- Catalytic Asymmetric Isomerizations of Alkynes To Allenes And Their Diastereoselective Functionalization Facilitated By An Organomanganese Auxiliary.
- Creator
- Roy, Animesh, Lepore, Salvatore D., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The present dissertation research is largely focused on the methods to synthesize highly substituted allene derivatives from alkynes in conjugation with carbonyl-containing functional groups. A key aspect of this research involves methylcyclopentadienylmanganese dicarbonyl (MMD), an inexpensive and air-stable organometallic auxiliary linked to alkynyl carbonyls via an η2-bond. This auxiliary influences bond formation to achieve enhanced stereoselectivity without itself undergoing any chemical...
Show moreThe present dissertation research is largely focused on the methods to synthesize highly substituted allene derivatives from alkynes in conjugation with carbonyl-containing functional groups. A key aspect of this research involves methylcyclopentadienylmanganese dicarbonyl (MMD), an inexpensive and air-stable organometallic auxiliary linked to alkynyl carbonyls via an η2-bond. This auxiliary influences bond formation to achieve enhanced stereoselectivity without itself undergoing any chemical transformation. Chapter 1 accounts various examples of such transition metal auxiliaries including MMD. Typically conjugated alkynyl carbonyls do not isomerize to thermodynamically less favored allenes. However, with the MMD auxiliary in place, alkynyl carbonyl compounds undergo facile 1,3-proton shifts in the presence of a mild base to produce allene isomers. Although allenyl aldehydes are important building blocks, we note that direct methods to prepare them nonracemically are not known. Chapter 2 describes the development of a new cinchonine-based phase transfer catalyst to access non-racemic allenyl aldehydes from MMD-complexed alkynyl aldehydes. With the manganese auxiliary in place, nonracemic allenyl aldehydes were obtained in a weakly basic biphasic reaction system via enantioselective protonation conditions. Chapter 3 describes the second use of the MMD auxiliary to direct nucleophilic addition reactions to allenyl aldehydes for the preparation of 2,3-allenols diastereoselectively. In the absence of the MMD auxiliary, nucleophilic reactions to the carbonyl group of axially chiral allenyl aldehydes is poorly diastereoselective, which is a long-standing problem. We observed that, in addition to leading to non-racemic allenyl aldehydes, the MMD auxiliary could also be used to improve diastereoselectivity in carbonyl additions due to its proximal position on the 2,3-bond of the allenyl aldehyde. Chapter 4 describes the use of allenyl esters as metathesis quenching agents. It was observed that the addition of an allenyl ester after a metathesis reaction was complete; facilitate the removal of most ruthenium metal impurities using simple silica chromatographic purification.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004918
- Subject Headings
- Transition metal catalysts., Stereochemistry., Chemistry, Organic., Chemistry, Physical and theoretical., Asymmetric synthesis.
- Format
- Document (PDF)
- Title
- Cyclic lipodepsipeptides as lead structures for the discovery of new antiobiotics.
- Creator
- Bionda, Nina., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
With antimicrobial resistance to current drugs steadily rising, the development of new antibiotics with novel mechanisms of action has become an imperative. The majority of life-threatening infections worldwide are caused by "ESKAPE" pathogens which are encountered in more than 40% of hospital-acquired infections, and are resistant to the majority of commonly used antibiotics. Naturally occurring cyclic depsipeptides, microbial secondary metabolites that contain one or more ester bonds in...
Show moreWith antimicrobial resistance to current drugs steadily rising, the development of new antibiotics with novel mechanisms of action has become an imperative. The majority of life-threatening infections worldwide are caused by "ESKAPE" pathogens which are encountered in more than 40% of hospital-acquired infections, and are resistant to the majority of commonly used antibiotics. Naturally occurring cyclic depsipeptides, microbial secondary metabolites that contain one or more ester bonds in addition to amide bonds, have emerged as an important source of pharmacologically active compounds or lead structures for the development of novel antibiotics. Some of those peptides are either already marketed (daptomycin) or in advanced stages of clinical development (ramoplanin). Structurally simple, yet potent, fusaricidin/LI-F and lysobactin families of naturally occurring antibiotics represent particularly attractive candidates for the development of new antibacterial agents capable of overco ming infections caused by multidrug-resistant bacteria. These natural products exhibit potent antimicrobial activity against a variety of clinically relevant fungi and Gram-positive bacteria. Therefore, access to these classes of natural products and their synthetic analogs, combined with elucidation of their mode of action represent important initial steps toward full exploitation of their antmicrobial potential. This dissertation describes a general approach toward the solid-phase synthesis of fusaricidin/LI-F and lysobactin analogs and an extensive structure-activity relationship (SAR) study. We have devised a simple and robust preparation strategy based on standard Fmoc solid-phase peptide synthesis protocols., The SAR study revealed key structural requirements for fusaricidin/LI-F and related cyclic lipopeptides antibacterial activity, including the presence of the guanidino moietly at the end of the lipidic tail, hydrophobic amino acid residues, and peptide conformation Moreover, substitution of the ester bond with an amide bond significantly improved stability under physiologically relevant conditions and reduced toxicity. In addition, we have shown that these antibacterial peptides exert their mode of action via a novel mechanism, which invloves bacterial membrane interactions, followed by peptide internalization. Altogether, the research described in this dissertation demonstrates that new antibiotics derived from fusaricidin/LI-F natural products, have the potential to meet the challenge of antibiotic resistance in Gram-positive bacteria.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/FAU/3360768
- Subject Headings
- Microbial peptides, Drugs, Design, Peptides, Therapeutic use, Genetic engineering, Antibacterial agents, Peptide antibiotics, Research, Methodology, Peptide antibiotics, Analysis
- Format
- Document (PDF)
- Title
- Development and applications of nucleophile assisting leaving groups (NALGs) with Titanium (IV) and Grignard reagents.
- Creator
- Li, Songye., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
We report here the development of very efficient aryl- and quinolinyl- sulfonate based leaving groups, termed Nucleophile Assisting Leaving Groups (NALGs), which substantially accelerate the rate of nucleophilic substitution reactions with metal halides. Detailed synthesis and kinetics study are described herein. Our synthesized NALGs have shown great reactivity towards poor nucleophiles and/or substrates traditionally considered too hindered to undergo nucleophilic attack. The abundant...
Show moreWe report here the development of very efficient aryl- and quinolinyl- sulfonate based leaving groups, termed Nucleophile Assisting Leaving Groups (NALGs), which substantially accelerate the rate of nucleophilic substitution reactions with metal halides. Detailed synthesis and kinetics study are described herein. Our synthesized NALGs have shown great reactivity towards poor nucleophiles and/or substrates traditionally considered too hindered to undergo nucleophilic attack. The abundant existence of halide, azide and amine in natural products demands new synthetic pathway. To fulfill this requirement, new mild stereoretentive halogenations (chlorination, bromination and iodination) reactions have also been developed for secondary cyclic alcohols using NALGs involving titanium (IV) reagents. The novel methodology can be extended to Azidation reactions as well with titanium (IV) azide, in which Ti (N3)4 is the first time being engaged in organic synthesis. Beased on the NALGs theory we discover the chlorosulfite can be a simplest NALG and applied as the intermediate in mild one-pot stereoretentive halogenations (chlorination and bromination) using titanium (IV) halides as catalysts or stoichiometric reagents. These reactions were found to be particularly efficient for cyclic alcohols. Finally, an efficient mild bromination and iodination reaction for primary and secondary alcohols with Grignard reagents is also reported. This reaction exhibits the generality with substrates with various leaving groups. The important features of this reaction are that, for the first time, bromide formation using Grignard reagents without the Cu (I) catalysts.
Show less - Date Issued
- 2011
- PURL
- http://purl.flvc.org/FAU/3183130
- Subject Headings
- Chemical kinetics, Chemical reaction, Condition and laws of, Organic compounds, Synthesis, Organotransition metal compounds, Intermediates (Chemistry), Organic reaction mechanisms
- Format
- Document (PDF)
- Title
- Development of Crown Ether Nucleophilic Catalysts (CENCs) and their Application in Rapid Fluorination of Silicon for PET Imaging & Diversification Reactions of γ-Silyl Allenyl Esters to All-carbon Quaternary Stereogenic Centers.
- Creator
- Jana, Susovan, Lepore, Salvatore D., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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In this dissertation, we discuss the development of new phase transfer agents, which are capable of rapid fluorination of silicon. These are 18-C-6 derivatives containing a hydroxyl group in the side arm (podand), also known as C-pivot lariats. The syntheses of these lariats including several that have not been previously reported and their efficient purification are described. The synthesis route leads to a robust and generalized approach to obtain these lariats on the gram scale. These...
Show moreIn this dissertation, we discuss the development of new phase transfer agents, which are capable of rapid fluorination of silicon. These are 18-C-6 derivatives containing a hydroxyl group in the side arm (podand), also known as C-pivot lariats. The syntheses of these lariats including several that have not been previously reported and their efficient purification are described. The synthesis route leads to a robust and generalized approach to obtain these lariats on the gram scale. These agents were initially designed for applications in positron emission tomography (PET). In this medical imaging modality, tracer agents containing silicon have found promising utility as fluoride receptors for more rapid radiolabeling. Phase transfer agents are generally required for 18F-labeling due to the low solubility in organic reaction media and reactivity of cyclotron-generated [18F]potassium fluoride. We envisioned that 18-C-6 derivatives may serve as both phase transfer agents as well as nucleophilic catalysts (CENCs). In this conception, CENCs were rapidly pre-complexed with KF followed by silicon fluorination, which takes advantage of a previously established silicon dianion mechanism. In collaboration with researchers at the NIH, we studied the effect of various linkers connecting the metal chelating unit to the nucleophilic hydroxyl group on the radiofluorination of silicon under mild condition. A hydrolysis resistant aryl silicon fragment has also been developed that contains various functional groups for convenient attachment to the potential PET radiotracer agents. In a second project, we demonstrate the unique reactivity of γ-silyl allenyl esters. Taking advantage of the silyl group as a fluoride acceptor, these allenoates readily underwent addition to a variety of carbon electrophiles, including aryl fluorides, to afford all-carbon quaternary centers bearing an ethynyl group. Surprisingly, in the presence of aldehydes, exclusive bis-substitution occurs at the γ-position to afford the dicarbinol. Details relating to reaction optimization and substrate scope for both the reactions are presented. Dicarbinol allenes were subsequently converted to highly substituted δ-lactones, a novel 6-hydro-2-pyrone as single diastereomers.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00013073
- Subject Headings
- Phase-transfer catalysis., Silicon., Positron-Emission Tomography., Crown ethers., Radioactive tracers., Fluorination.
- Format
- Document (PDF)
- Title
- Development of Nucleophile Assisting Leaving Groups (NALGs) and new stereoselective reactions using titanium(IV) reagents.
- Creator
- Mondal, Deboprosad., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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We report here the development of very efficient sulfonate based leaving groups, termed Nucleophile Assisting Leaving Groups (NALGs), to accelerate the rate of nucleophilic substitution reactions involving poor nucleophiles and/or substrates traditionally considered too hindered to undergo nucleophilic attack. Indeed NALGs have shown exceptional ability in improving rate of nucleophilic substitution reactions. New very mild stereoretentive halogenations and azidation reactions have also been...
Show moreWe report here the development of very efficient sulfonate based leaving groups, termed Nucleophile Assisting Leaving Groups (NALGs), to accelerate the rate of nucleophilic substitution reactions involving poor nucleophiles and/or substrates traditionally considered too hindered to undergo nucleophilic attack. Indeed NALGs have shown exceptional ability in improving rate of nucleophilic substitution reactions. New very mild stereoretentive halogenations and azidation reactions have also been developed for secondary cyclic alcohols using NALGs involving titanium(IV) reagents. This reaction is particularly significant since the carbon-halogen bond is found widely in natural products and is used extensively as a synthesis intermediate. Azide is also a synthetically important functional group from which a variety of biologically important functional groups are conveniently obtained. Though stereoretentive chlorination and bromination reactions are known, we have developed, for the first time, a stereoretentive azidation reaction using titanium(IV) azide, a reagent not previously used in organic synthesis. During our development of stereoretentive reactions, we eventually developed very efficient, mild, two-step one-pot stereoretentive halogenations (chlorination and bromination) using titanium(IV) halides as catalysts or stoichiometric reagents. These reactions were found to be particularly efficient for cyclic alcohols. An efficient one pot stereoretentive amidation reaction for secondary cyclic alcohols is also reported. The important features of this reaction are that, for the first time, chlorosulfite (prepared in situ from alcohol using thionylchloride) has been used as a leaving group and titanium(IV) fluoride as an activator., Utilization of those two reagents is unique as thionylchloride has never been used for nucleophilic substitution reactions except in chlorination procedures. In addition, this work has found new and creative applications for titanium (IV) fluoride, a reactant rarely used in organic synthesis. Further exploiting the unique reactivity of titanium(IV), reactions of alkenes with various nucleophiles have been developed with this reagent in both catalytic and stoichiometric quantities. It was observed that a-substituted aromatic conjugated alkenes dimerize to generate important indan class of compounds which are very important in the polymer industry. In addition, non conjugated unactivated alkenes react with various nucleophiles to yield the adduct.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/3159264
- Subject Headings
- Chemical reaction, Condition and laws of, Organic compounds, Synthesis, Chemical templates, Intermediates (Chemistry), Organotransition metal compounds, Organic reaction mechanisms
- Format
- Document (PDF)