Organic Chemistry Commons^™

Aptamer Selection And Development Of Electrochemical Aptamer-Based Sensors For Neuropeptide Y, Evelyn Adela Carreto Guevara

Department of Chemistry: Dissertations, Theses, and Student Research

In this thesis, we report the results of four aptamers obtained from an aptamer selection process called the systematic evolution of ligands by exponential enrichment (SELEX) with affinity to Neuropeptide Y (NPY). NPY is a highly abundant peptide transmitter with widespread distribution throughout the body which affects various physiological functions. These functions include energy homeostasis, appetite regulation, stress response, and anxiety regulation. Dynamic monitoring of NPY levels is crucial for better understanding behaviors in individuals with neurological disorders associated with NPY. Aptamers are synthetic oligonucleotides obtained through SELEX which have a binding affinity to a target of interest when in …

Synthesis And Study Of High-Spin Stable Organic Radicals For Electrical Conductors And Mannosamine Nitroxide For Mri Contrast Agents, Shuyang Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

In the first project, we describe the synthesis of an ambient stable high spin organic diradical 4 based on the Blatter moiety. The high-spin (S = 1) organic diradical 4, which consists of two Blatter radical moieties in a conjugated structure, exhibits a nearly exclusive population (88%) on triplet ground state at room temperature as a consequence of a large single-triplet energy gap (ΔEST = 0.5 kcal/mol). The target diradical molecule is synthesized over five steps with structural confirmation by single-crystal X-ray diffraction. The thermogravimetric analysis (TGA) shows the onset of decomposition at ~264 oC, indicating the diradical molecule has …

Issue Of False Amphetamine Field Test Positives Caused By Sugar: Use Of Baeyer Test As A Secondary Test Solution, Reed A. Knutson, Jennah Duncan, Kara Peightal, Samuel Thomas

Department of Chemistry: Dissertations, Theses, and Student Research

The Marquis reagent is a well-established and widely used chemical presumptive test for 3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine. It is composed of concentrated sulfuric acid and 40% formaldehyde, which act upon alkaloids causing them to complex into larger molecules. This complexation causes a color change that can be visually interpreted as a positive or negative result. Almost any sugar molecule can be complexed in this way as well, due to their many OH groups. Experimentally it was found that the sugar molecules did complex with one another when the Marquis test was administered. The color produced by this reaction was brownish-red. …

C(Sp2)-C(Sp3) Cross-Coupling Of Aryl Halides And Active C(Spp3)-H Bonds Via Dual Catalysis: Organic Photocatalysis/Nickel Redox Catalysis, Nicholas Armada

Department of Chemistry: Dissertations, Theses, and Student Research

Convenient catalytic methodologies that can facilitate the formation of C-C bonds are undoubtedly of great interest in synthetic organic chemistry. Recent reports in literature have showcased hybrid catalytic methods that couple Ni-redox catalysis and photocatalysis to enable C-H activation of tetrahydrofuran (THF) and subsequent cross-coupling with aryl halides in appreciable yields and under relatively mild reaction conditions.^1-2 However, these studies used expensive, heavy metal-containing photocatalysts and both report difficulty obtaining low-specificity across their scopes of aryl-halides. The following report will shed light on a class of photo-excitable small organic molecules that – in conjunction with a catalytic Ni-redox cycle …

Design And Synthesis Of Stable Aminyl And Nitroxide Radical Precursors, Joshua Bryan Lovell

Department of Chemistry: Dissertations, Theses, and Student Research

Aminyl diradicals with sterically-hindered tert-butyl groups have yet to be fully investigated for their increased stability due to their difficulty in synthesis. The first chapter of this thesis details design and synthesis towards sterically-hindered aminyl radical and diradical precursors.

Structural features effecting nitroxide radical stability have been well investigated except for the impact on the ring-size of stability of nitroxides towards reduction by ascorbate. Two 7-membered nitroxides derived from TEMPONE and TEMPOL have been synthesized and characterized. The alcohol nitroxide shows increased stability towards reduction by ascorbate compared to the corresponding TEMPOL, while the other nitroxide shows decreased stability compared …

Phosphonate-Directed Catalytic Asymmetric Hydroboration: Synthesis Of Functionalized Chiral Secondary And Tertiary Boronic Esters And Mechanistic Insights, Suman Chakrabarty

Department of Chemistry: Dissertations, Theses, and Student Research

Over the past 30 years, catalytic asymmetric hydroboration (CAHB) of alkenes has emerged as a leading methodology to access chiral primary and secondary boronic esters. However, it wasn’t until 2015 that directed-CAHB was for the first time shown to efficiently access chiral tertiary boronic esters. The latter are excellent precursors to synthetically challenging structural motifs such as chiral tertiary alcohols, carbinamines and all-carbon quaternary stereocenters via stereospecific C-B bond substitutions. This dissertation focuses on phosphonate-directed CAHB of diverse alkene substrates, including challenging stereodefined trisubstituted alkenes, to efficiently access multifunctional chiral secondary and tertiary boronic esters. Mechanistic insights obtained via deuterium …

Developing Functionalized Peroxide Precursors For The Synthesis Of Cyclic And Spirocyclic Ethers, Anna J. Diepenbrock

Department of Chemistry: Dissertations, Theses, and Student Research

There is increasing interest in the development of methods for the synthesis of oxetanes and spirocyclic oxetanes, a class of molecules of interest to chemists as they synthesize libraries of possible drug target scaffolds with tunable physiochemical and biological properties.^1,2 Although most ethers are prepared through reaction of nucleophilic oxygen with electrophilic carbon, this work explores new reagents and routes for the synthesis of spirocyclic oxetanes based upon an application of "umpolung" or polarity reversal involving attack of nucleophilic carbon on the electrophilic oxygen of a peroxide (Scheme 1). In this work, a 2-carbon peroxide synthon for reverse etherification …

Enantioselective Γ- And Δ -Borylation Of Unsaturated Carbonyl Derivatives: Synthesis, Mechanistic Insights, And Applications, Gia L. Hoang

Department of Chemistry: Dissertations, Theses, and Student Research

Chiral boronic esters are valuable synthetic intermediates widely used in a variety of stereospecific transformations. Transition metal-catalyzed asymmetric hydroboration (CAHB) of alkenes is among the most popular methods for their preparation. Enantioselective hydroboration of activated alkenes (i.e., vinyl arene derivatives or conjugated carbonyl compounds) have been extensively studied by many research groups. We, on the other hand, are interested in enantioselective hydroboration of unactivated alkenes utilizing coordinating functional groups (e.g., carbonyl derivatives) to give functionalized, chiral boronic esters. While conjugate addition and C–H activation methodologies provide efficient alternatives to CAHB for enantioselective beta-borylation of carbonyl compounds, direct gamma- and delta-borylations …

Studies In Directed Catalytic Asymmetric Hydroboration Of 1,2-Disubstituted Unsaturated Amide, Shuyang Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

The Rh-catalyzed, substrate directed catalytic asymmetric hydroboration of γ,δ-unsaturated amides provides a direct route to enantioenriched acyclic secondary γ-borylated carbonyl derivatives with high regio- and enantioselectivity. The catalytic condition optimization and substrate scope study is discussed, including the effects in catalytical asymmetric hydroboration on pre-installed chiral γ,δ-unsaturated amides. A mechanistic study from kinetic approach by graphical manipulation (reaction progress kinetic analysis for substrate orders and normalized time analysis for catalyst order.) was discussed in this thesis

Advisor: Professor James M. Takacs

Genetically Encoded Fluorescent Protein Biosensor For Nitric Oxide, Wenjia Zhai

Department of Chemistry: Dissertations, Theses, and Student Research

Nitric oxide (NO) is an important molecule in living cells for signaling, thus a specific sensor to detect its level in live cells is needed. Currently there are a few small molecule probes for the detection of NO. A common shortcoming of these probes is their unavoidable leakage from the target cells. In this project, I seek to develop a novel green fluorescent protein (GFP)-based biosensor to detect cellular NO. This GFP-based sensor is genetically encodable and can potentially avoid the possible false positive result due to the leakage. I synthesized an unnatural amino acid (unAA) and examined its incorporation …

Design And Synthesis Of Novel Octacarboxy Porphyrinic Metal–Organic Frameworks, Jacob A. Johnson

Department of Chemistry: Dissertations, Theses, and Student Research

Metal-Organic Frameworks (MOFs) are a class of nanoporous crystalline materials constructed via the interconnection between metal-ions/inorganic clusters and organic ligands. Since the surface area, pore size and distribution, and chemical functionalities of MOFs are highly tunable via the judicious combinations of inorganic clusters and organic ligands, MOFs have attracted intensive interests for a variety of applications including gas adsorption and separation, catalysis, chemical sensing, and drug delivery among others. Porphyrin based ligands are of particular interest for building functional MOFs due to their unique photo-, electro-, and catalytic properties. In addition, the four-fold symmetry of porphyrin ligands offers an effective …

Thermolysis Of Hypervalent Iodine Complexes: Synthesis Of Fluorinated Radiotracers For Positron Emission Tomography And Synthesis Of Quaternary Α-Alkyl Α-Aryl Amino Acids, Jayson J. Kempinger

Department of Chemistry: Dissertations, Theses, and Student Research

Hypervalent iodine complexes can be used to deliver a variety of functional groups to arenes. Delivery of fluorine‑18, in a manner compatible with positron emission tomography (PET), is especially attractive. Vizamyl^TM, an injectable solution of [¹⁸F]Flutemetamol, is currently used to diagnose and monitor the progression of Alzheimer’s Disease (AD), the most common form of dementia. AD affects 47.5 million people across the world as of 2015, and is projected to affect 1 in 85 people by 2050. An improved radiosynthesis of [¹⁸F]Flutemetamol via a diaryliodonium salt is described. The use of nonpolar solvents minimizes …

Selective Iodination Using Diaryliodonium Salts, William H. Miller Iv

Department of Chemistry: Dissertations, Theses, and Student Research

Aryl iodides have become widely recognized as versatile synthetic intermediates, owing to aromatic iodine’s excellent ability to participate in oxidative addition reactions. Iodoarenes readily undergo a variety of synthetic transformations including metal catalyzed cross-coupling reactions, diaryliodonium chemistry, formation of organometallics through reduction or metal-halogen exchange, as well as classical S_N2 type chemistry. Because a wide array of transformations are available for aryl iodides, organic molecules containing this moiety often serve as vital precursors to highly desirable pharmaceuticals.

This thesis describes a simple and selective two-step approach to the formation of aryl iodides. This method proceeds through an easily …

Synthesis And Applications Of Cyclobutenes, Benjamin Enns

Department of Chemistry: Dissertations, Theses, and Student Research

Our group is interested in cyclobutene analogs of fatty acids as reactive coatings, potential antibiotics, and as a new class of bioconjugate linkers. A convenient synthesis of this class of molecules was previously reported from our lab. However, ammonia, a key reagent in the earlier route, was recently reclassified as a highly corrosive gas requiring highly specialized equipment for storage and handling. The goal of this research was to find a convenient synthesis for the formation of cyclobutene that did not involve the use of ammonia. The other part of this thesis describes the preparation of a short chain cyclobutene …

Toward The Probing Of Dhqs Activity By Protein Engineering Through The Introduction Of Unnatural Amino Acids And The Selection Of Trna/Trna Synthetase Pairs, Shaina E. Ives

Department of Chemistry: Dissertations, Theses, and Student Research

Protein engineering is a valuable tool that allows scientist to explore how an enzyme works by mutation of key residues. This method has been used to improve function or stability of enzymes, thus allowing their use in both the lab and in industry to be expanded. Genetic incorporation of unnatural amino acids (unAA) can be used with protein engineering to exceed the current limitations, due to the limited number of functional groups of the 20 common amino acids.

The majority of this thesis will discuss the progress on incorporating the various unAA into the active site of the enzyme, Dehydroquinate …

Selective Iodination Using Diaryliodonium Salts, William H. Miller Iv

Department of Chemistry: Dissertations, Theses, and Student Research

Aryl iodides have become widely recognized as versatile synthetic intermediates, owing to aromatic iodine’s excellent ability to participate in oxidative addition reactions. Iodoarenes readily undergo a variety of synthetic transformations including metal catalyzed cross-coupling reactions, diaryliodonium chemistry, formation of organometallics through reduction or metal-halogen exchange, as well as classical S_N2 type chemistry. Because a wide array of transformations are available for aryl iodides, organic molecules containing this moiety often serve as vital precursors to highly desirable pharmaceuticals.

This thesis describes a simple and selective two-step approach to the formation of aryl iodides. This method proceeds through an easily …

The 8-Silyloxyquinoline Scaffold As A Versatile Platform For The Sensitive Detection Of Aqueous Fluoride, Xinqi Zhou

Department of Chemistry: Dissertations, Theses, and Student Research

As one of the most essential elements in nature, fluoride has been well known and extensively studied since the 16^th century. Since then the two-edged nature of fluoride in biological systems has been well described. Specifically, moderate fluoride exposure can aid in tooth and bone development, while fluoride overexposure results in the depilating disease known as fluorosis. Because of the side effects upon overexposure of fluoride, there is a need to develop fast and straight forward methods to sensitively and selectively detect and quantify fluoride concentration in drinking water. With this goal in mind and by taking advantage of …

New Methods For Synthesis Of Organic Peroxides And Application Of Peroxide Electrophiles To Synthesis Of Functionalized Ethers, Shiva Kumar Kyasa

Department of Chemistry: Dissertations, Theses, and Student Research

New Method for Synthesis of Alkyl Hydroperoxides: There are a number of methods reported for synthesis of alkyl hydroperoxides, but most of them suffer either from poor yields or the formation of unwanted side products. I will be discussing new methodology for efficient synthesis of pure samples of 1° and 2° alkyl hydroperoxides via alkylation of readily available cyclododecanone 1,1-dihydroperoxide followed by hydrolysis of the resulting bis peroxyacetals.

Peroxide Electrophiles for Synthesis of Functionalized Ethers: Peroxides are underexplored functional groups as precursors for C-O bond formation and ether synthesis. The reactivity of dialkyl peroxides towards organometallics such as alkyl lithium …

Hydrolytically Stable Analogues Of Sugar Phosphates And A Miniaturized In Situ Enzymatic Screen, Xiang Fei

Department of Chemistry: Dissertations, Theses, and Student Research

The glmS riboswitch undergoes self-cleavage upon binding its metabolic product GlcN6P, thereby providing a negative feedback mechanism limiting translation of the glmS protein when GlcN6P is abundant. As a first step toward the development of novel antimicrobials, we have synthesized a series of GlcN6P analogues bearing phosphatase-inert surrogates in place of the natural phosphate ester functionality. The self-cleavage assay identified two such compounds that display significant riboswitch actuator activity; namely those bearing a 6-phosphonomethyl group or a 6-O-malonyl ether. These two analogues exhibit a 22-fold and a 27-fold higher catalytic efficiency, respectively, than does glucosamine. Docking experiments were …

Studies In Asymmetric Synthesis: Supramolecular Catalysis, C–H Activation, And D-Cycloserine Synthesis, Nathan C. Thacker

Department of Chemistry: Dissertations, Theses, and Student Research

Rh-catalyzed asymmetric hydrogenation has emerged as a powerful tool for the manufacturing of chiral pharmaceuticals. While the mechanism is well understood, catalyst design a priori is not yet possible. Supramolecular catalysis, the use of non-covalent forces to affect a catalytic process, can afford the catalyst diversity required to uncover efficient catalysts and further our understanding. Using a modular design and self-assembly, a large scale supramolecular catalyst screening in a catalyst scaffold optimization study of rhodium-catalyzed asymmetric hydrogenation was carried out. Analyzing the data yields some new insights into the roles of each module making up the supramolecular catalyst. Perhaps most …

A, Catalysis Of Co-Prox By Water-Soluble Rhodium Fluorinated Porphyrins. B, Studies Toward Fluorination Of Electron Rich Aromatics By Nucleophilic Fluoride, Shri Harsha Uppaluri

Department of Chemistry: Dissertations, Theses, and Student Research

The rhodium(III) derivative of a water soluble, heavily fluorinated porphyrin is shown to catalyze the low temperature, low pressure selective oxidation of carbon monoxide in hydrogen gas streams for use in fuel cell applications. The catalytic activity is a direct result of the removal of electron density from the metal center. Selectivity for CO oxidation is a direct consequence of fluorination of the porphyrin periphery, since these substituents enhance the rate of the reaction and prevent the formation of Rh(II)-Rh(II) dimmers. Significantly, the dramatic increase in rhodium hydride acidity caused by fluorination precludes hydrogen activation and generation, thereby permitting preferential …

Investigations Of Inter- And Intramolecular C-O Bond Forming Reactions Of Peroxide Electrophiles, Benjamin W. Puffer

Department of Chemistry: Dissertations, Theses, and Student Research

A common reaction to yield ethers relies on an alkoxide nucleophile and a carbon electrophile (Williamson ether formation). Ethers can also be formed by reactions with carbon nucleophiles and oxygen electrophiles by way of the peroxide functional group. We screened a number of carbon nucleophiles suitable for attack on dialkyl peroxides to form new C-O bonds. Also a novel approach using a peroxyketal electrophile is shown to increase the efficiency of this intermolecular reaction. This method of C-O bond formation can also be implemented intramolecularly, not seen before in the literature, to yield cyclic ethers. This approach requires the generation …

The Use Of Rhenium(Vii) Oxide As A Catalyst For The Substitution Of Hemiacetals, Michael W. Richardson

Department of Chemistry: Dissertations, Theses, and Student Research

Rhenium (VII) oxides have proven to be mild and versatile catalysts in organic chemistry. They have previously been utilized to catalyze the transposition of allylic aclohols, Prins reaction, and reductive amination to name a few examples. This thesis reports the application of Re(VII) oxide in the substitution of hemi-acetals with a wide array of nucleophiles including oxo-, thio-, and peroxy-nucleophiles. These reactions proceed efficiently with rapid reaction times and high yields.

Adviser: Patrick H. Dussault

I, Synthesis Of Β-Sitosterol And Phytosterol Esters. Ii, New Methodology For Singlet Oxygen Generation From 1,1-Dihydroperoxides, Jiliang Hang

Department of Chemistry: Dissertations, Theses, and Student Research

Phytosterols are steroid compounds structurally similar with cholesterol and vary in the nature of carbon side chain. β-Sitosterol is commercially available in preparative amount only as mixtures with other phytosterols. New semipreparative synthesis of pure β-sitosterol and sidechain-modified phytosterols is discussed in this dissertation. This new synthesis is achieved via a temporary masking of the stigmasterol 5,6-alkene as an epoxide. Following performance of the desired modification, the alkene is regenerated through a mild deoxygenation. Preparation of phytosterol esters for cholesterol metabolism study is also discussed in this dissertation.

Singlet oxygen (¹O₂) is the lowest excited state …

Rhodium-Catalyzed Hydroboration Of 1,1-Disubstituted Alkenes, Scott A. Pettibone

Department of Chemistry: Dissertations, Theses, and Student Research

Enantioselective rhodium-catalyzed hydroboration is becoming an increasingly important asymmetric transformation of alkenes based upon the utility of the organo boranate ester intermediate. The newly acquired asymmetric C-B bond can be converted to C-O, C-N, C-C bonds and the organo borante can be coupled to SP2 hybridized halogen bonds, all with retention of configuration. Catalyzed hydroboration of 1,1-disubstituted alkenes are an especially challenging substrate class for this enantioselective transformation. The difficulty for catalysts to distinguish between the two enantiotopic faces of the olefin is one of the major issues that have to be overcome to achieve a desirable level of enantioselectivity. …

High Yield Synthesis Of Positron Emission Tomography Ligands For Metabotropic Glutamate Receptor Imaging, Saraanne E. Hitchcock

Department of Chemistry: Dissertations, Theses, and Student Research

Positron Emission Tomography (PET) is a powerful and non-invasive imaging technique used for human and animal organ imaging. Currently, the market for PET is project to reach $5.4 billion per year by 2015.5 This research focuses on the direct incorporation of [18F]-fluoride into PET ligands. The widespread use of PET imaging is currently frustrated, in part, by the lack of efficient fluorination chemistry.

Glutamate, one of the 20 most abundant naturally occurring amino acids, serves as a neurotransmitter in the central nervous system. Glutamate functions in this capacity by binding to ionotropic and metabotropic receptors. Metabotropic receptors are Gcoupled proteins …

I, An Improved Procedure For Alkene Ozonolysis. Ii, Exploring A New Structural Paradigm For Peroxide Antimalarials., Charles Edward Schiaffo

Department of Chemistry: Dissertations, Theses, and Student Research

The use of ozone for the transformation of alkenes to carbonyls has been well established. The reaction of ozone with alkenes in this fashion generates either a 1,2,4-trioxolane (ozonide) or a hydroperoxyacetal, either of which must undergo a separate reduction step to provide the desired carbonyl compound. There is considerable interest in being able to perform a reductive ozonolysis to directly provide the carbonyl. Previous reports from the Dussault lab have shown that amine N-oxides are able to perform a reductive ozonolysis. In the course of efforts to expand this reaction to other oxyanions it was realized that water was …

Ultrasonic Activation Of Triacetone Triperoxide, Latravia R. Dobson

Department of Chemistry: Dissertations, Theses, and Student Research

Triacetone triperoxide (TATP) is an organic peroxide that has received widespread attention in recent years. TATP is a ketone peroxide with a high active oxygen content. It is relatively shock sensitive, with explosive decomposition easily initiated, and is therefore considered a primary explosive. However, TATP is also a powerful explosive possessing about 83 % of the power of TNT. TATP can be prepared quickly and easily from inexpensive household chemicals in the absence of any specialized facilities, making it the explosive of choice for modern day terrorists. TATP poses a major challenge for security and law enforcement services around the …

I, A New Synthetic Approach To The Synthesis Of N-(Phosphonoacetyl)-L-Ornithine. Ii, The Influence Of Pyridine On The Ozonolysis Of Alkenes, Bradley M. Johnson

Department of Chemistry: Dissertations, Theses, and Student Research

Part I. The use of chemical inhibitors to manipulate the level of amino acids in cells has proven to be invaluable in the mechanistic study of gene expression in bacteria and fungi. Here we present a new approach to the synthesis of δ‐N‐ (phosphonoacetyl)‐L‐ornithine (PALO), a potent ornithine transcarbamylase inhibitor, using a new amino acid protecting group, 9‐borabicyclononane (9‐BBN). Starting from commercially available reagents and utilizing mild reaction conditions, we were able to form PALO in fewer synthetic steps and in greater yields than previous attempts.

Part II. Ozonolysis is widely used to transform alkenes into oxygen‐rich functional groups (e.g.– …

I, Development Of The In Situ Reductive Ozonolysis Of Alkenes With Tertiary Amine N-Oxides. Ii, Progress Toward The Asymmetric Synthesis Of Peroxyplakoric Acid A3, Christopher P. Schwartz

Department of Chemistry: Dissertations, Theses, and Student Research

Ozone, first discovered in the mid 1800’s, is a triatomic allotrope of oxygen that is a powerful oxidant. For over a century, research has been conducted into the synthetic application and mechanism of reactions of ozone with organic compounds. One of the major areas of interest has been the ozonolysis of alkenes. The production of carbonyl compounds is the most common synthetic application of ozonolysis. The generally accepted mechanism developed by Rudolf Criegee for this reaction involves the 1,3-electrocyclic addition of ozone to the π bond of the alkene to form a 1,2,3-trioxolane or primary ozonide. The primary ozonide is …