Organic Chemistry Commons^™

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Transition Metal Catalysis And The Synthesis Of Biologically Interesting Heterocycles: A Study Of Gold-Catalyzed Intermolecular Cyclization And Palladium-Catalyzed Suzuki Cross-Coupling, Alexandria E. Weber

Undergraduate Honors Thesis Projects

Two methods of transition metal catalysis were investigated as a means to synthesize biologically interesting heterocyclic molecules. The gold-catalyzed intermolecular cyclization of allenes and 1,3-dipoles was first explored. An allene, ethyl-3-hexyl-3,4-pentadienoate was subjected to a combination of one of five 1,3-dipoles ((Z)-N-benzylidenemethanamine oxide, 1-benzylidene-3-oxopyrazolidin-1-ium-2-ide, (Z)-N-benzylidenebenzenamine oxide, (E)-N-benzylidenebenylamine, and (E)-N-Benzylidene-4-methoxybenzenamine) and one of three gold catalysts (1,3-bis(2,6-di-isopropylphenyl)imidazole-2-ylidenegold(I)chloride, chlorotriphenyl-phosphinegold(I), and gold(III) chloride). No heterocyclic product resulted from these catalytic reactions. The palladium-catalyzed Suzuki cross-coupling reaction of a 1,3,4-oxadiazole (3-(5-(4-(bromo)phenyl)-1,3,4-oxadiazol-2-yl)pyrazine-2-amine) with phenyl boronic pinacol ester was then explored, varying whether the 1,3,4-oxadiazole was unprotected or …

Investigating The Synthesis Of Heterocycles Via Gold Catalyzed Cyclizations And Cyclo-Dehydrating Reactions, Katherine L. Childers

Undergraduate Honors Thesis Projects

The goal of this project was to study novel synthetic procedures for heterocycles. This was achieved through a two-part investigation. In the first part, a variety of conditions for the gold catalyzed cyclization of allenes were studied. This work was focused on the lesser studied intermolecular reactions of allenes. A variety of allenes were synthesized, and then reacted with 1,3-dipoles and a gold catalyst. These reactions were determined to be unsuccessful through the analysis of nuclear magnetic resonance spectroscopy data. In the second part of this study, the synthesis of 1,3,4-oxadiazoles was investigated. Several cited procedures were examined to determine …

Bond Length - Bond Valence Relationships For Carbon - Carbon And Carbon - Oxygen Bonds, C. Harris, F. D. Hardcastle

Journal of the Arkansas Academy of Science

In the present study, relationships are developed for determining bond orders (also referred to as bond valences or bond numbers) from published bond lengths for carbon-carbon (C-C) and carbon-oxygen (C-O) bonds. The relationships are based on Pauling’s empirical formula s = exp((Ro-R)/b)), where s is the bond order, R is the corresponding bond length, Ro is the unit valence bond length, and b is a fitting parameter. We use a recently derived relationship for the b parameter in terms of the bonding atoms’ published atomic orbital exponents. The resulting equations were checked against published x-ray diffraction (XRD) data for 176 …

Wave Profile For Anti-Force Waves With Maximum Possible Currents, M. Hemmati, R. Horn, W. P. Childs, A. K. Meredith

Journal of the Arkansas Academy of Science

In the theoretical investigation of the electrical breakdown of a gas, we apply a one-dimensional, steady state, constant velocity, three component fluid model and consider the electrons to be the main element in propagation of the wave. The electron gas temperature, and therefore the electron gas partial pressure, is considered to be large enough to provide the driving force. The wave is considered to have a shock front, followed by a thin dynamical transition region. Our set of electron fluid-dynamical equations consists of the equations of conservation of mass, momentum, and energy, plus the Poisson's equation. The set of equations …

Friedel–Crafts Hydroxyalkylation Of Indoles Mediated By Trimethylsilyl Trifluoromethanesulfonate, C. Wade Downey, Christopher D. Poff, Alissa N. Nizinski

Chemistry Faculty Publications

Indoles and N-alkylindoles undergo Friedel–Crafts addition to aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate and a trialkylamine to produce 3-(1- silyloxyalkyl)indoles. Neutralization of the reaction mixture with pyridine followed by deprotection under basic conditions with tetrabutylammonium fluoride provides the 1:1 adduct as the free alcohol. This method prevents spontaneous conversion of the desired products to the thermodynamically favored bisindolyl(aryl)methanes, a process typically observed when indoles are reacted with aldehydes under acidic conditions.

Total Synthesis Of Clavatadine A Analogs To Produce A Viable Reversible Inhibitor For Factor Xia, Christopher E. Malmberg

All Master's Theses

Cardiovascular disease has quickly become a major health concern in the United States, with numerous citizens dying from cardiovascular disease each year. Older medications, while effective against cardiovascular disease, are problematic to prescribe. A recently isolated natural product, clavatadine A, selectively inhibits human blood coagulation factor XIa. As a result, the synthesis and biological testing of clavatadine A and synthetic clavatadine A analogues that selectively inhibit factor XIa would represent a new direction in cardiovascular disease research. A potent and selective factor XIa inhibitor has the potential to be a safer replacement for current anticoagulants, such as Warfarin, Pradaxa^{® …}

Design And Development Of Bodipy-Based Fluorescent Probes For Sensing And Imaging Of Cyanide, Zn (Ii) Ions, Lysosomal Ph And Cancer Cells, Jingtuo Zhang

Dissertations, Master's Theses and Master's Reports - Open

BODIPY (4,4-Difluoro-3a,4a-diaza-s-indacene) dyes have gained lots of attention in application of fluorescence sensing and imaging in recent years because they possess many distinctive and desirable properties such as high extinction coefficient, narrow absorption and emission bands, high quantum yield and low photobleaching effect. However, most of BODIPY-based fluorescent probes have very poor solubilities in aqueous solution, emit less than 650 nm fluorescence that can cause cell and tissue photodamages compared with bio-desirable near infrared (650-900 nm) light. These undesirable properties extremely limit the applications of BODIPY-based fluorescent probes in sensing and imaging applications. In order to overcome these drawbacks, we …

Effect Of Methoxy Substituents On The Activation Barriers Of The Glutathione Peroxidase-Like Mechanism Of An Aromatic Cyclic Seleninate, Craig A. Bayse, Ashley L. Shoaf

Chemistry & Biochemistry Faculty Publications

Density functional theory (DFT) models including explicit water molecules have been used to model the redox scavenging mechanism of aromatic cyclic seleninates. Experimental studies have shown that methoxy substitutions affect the rate of scavenging of reactive oxygen species differently depending upon the position. Activities are enhanced in the para position, unaffected in the meta, and decreased in the ortho. DFT calculations show that the activation barrier for the oxidation of the selenenyl sulfide, a proposed key intermediate, is higher for the ortho methoxy derivative than for other positions, consistent with the low experimental conversion rate.

Proton-Electrostatic Localization: Explaining The Bioenergetic Conundrum In Alkalophilic Bacteria, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The decades-longstanding energetic conundrum of alkalophilic bacteria as to how they are able to synthesize ATP has now, for the first time, been clearly solved using the proton-electrostatics localization hypothesis. This is a major breakthrough advance in understanding proton-coupling bioenergetics over the Nobel-prize work of Peter Mitchell’s chemiosmotic theory. The widespread textbook Mitchellian proton motive force (pmf) equation has now been significantly revised. Use of the newly derived equation results in an overall pmf value (215~233 mV) that is more than 4 times larger than that (44.3 mV) calculated from the Mitchellian equation for the alkalophilic bacteria growing at pH …

Experimental Demonstration Of Localized Excess Protons At A Water-Membrane Interface, Haitham A. Saeed, James W. Lee

Chemistry & Biochemistry Faculty Publications

The widespread Mitchellian proton motive force equation has recently been revised with the proton-electrostatics localization hypothesis, which, for the first time, successfully elucidates the 30-year longstanding energetic conundrum of ATP synthesis in alkalophilic bacteria. To demonstrate the fundamental behavior of localized protons in a pure water-membrane-water system in relation to the newly derived pmf equation, excess protons and excess hydroxyl anions were generated by utilizing an "open-circuit" water-electrolysis system and their distributions were tested using a proton-sensing aluminum membrane. The proton-sensing film placed at the membrane-water interface displayed dramatic localized proton activity while that placed into the bulk water phase …

Synthesis Of Benzofused-P-Indolequinones From 1,4-Naphthoquinone And Selective N-Debenzylation By Dess-Martin Periodinane, Quang Huynh Luu

Open Access Theses & Dissertations

p-Indolequinones are important heterocycles since they display interesting bioactivities such as anticancer activities as well as the ability to trigger drug release in drug targeting research. Additionally, they are also useful in precursors for the synThesis of bioactive compounds. Over decades, many methodologies have been investigated for the synThesis of p-indolequinones. Among those, cyclization of quinones plays an important role in convenient synThesis of these compounds. However, the great majority of these methods only describe quinones as electrophiles in cyclization. In our research, we found an intramolecular nucleophilic attack of quinone to an in-situ generated carbonyl group and developed a …

Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce

Williams Honors College, Honors Research Projects

Several aldehydes (butanal, pentanal, hexanal, 4-hydroxybenzaldehyde) were reacted with 1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (1) to produce novel C² substituted imidazolium salts for the potential use against non-small cell lung cancer in humans. Compounds 2-(1-hydroxypentyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (3) and 2-(1-hydroxyhexyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (5) were successfully synthesized with structures supported by NMR and mass spectrometry. Characterization by ¹H NMR showed evidence of 1 in both compounds. The tumor cell growth inhibition of 3 against non-small cell lung cancer lines NCI-A549, NCI-H460, HCC827, and NCI-H1975 was tested and found to be comparable to cisplatin as measured by MTT assay. …

Synthetic Study Of Karlotoxins And Investigation Of Alpha-Diaminoboryl Carbanion Chemistry, Yusuke Takahashi

Electronic Theses and Dissertations

Karlotoxins (KmTxs), produced by a toxic marine/estuarine phytoplankton, the dinoflagellate Karlodinium veneficum, are known to be ichthyotoxic, thus being associated with numerous fish deaths events worldwide. They have also been reported to show a variety of biological activities such as hemolytic, cytotoxic, and anti-fungal activities. Recently, the Hamann group successfully assigned the absolute configurations of KmTx2, the first complete structure elucidation among the congeners. In a structural sense, karlotoxins are a family of linear polyketides with three distinctive regions; a bis-tetrahydropyran core fragment, a long, highly oxygenated carbon chain, and a lipophilic chlorodiene unit. Such potent biological activities as well …

Synthesis And Anti-Proliferative Activity Of N,N’-Bis(Arylmethyl)Benzimidazolium Salts, Travis M. Williams

Williams Honors College, Honors Research Projects

A series of N,N’-bis(arylmethyl)benzimidazolium salts with hydrophilic and lipophilic substituents have been synthesized, characterized, and tested against select non-small cell cancer cell lines. Substituent variations on the imidazole ring have shown that lipophilicity and hydrophilicity can influence the imidazolium salts’ anti-proliferative activity and aqueous solubility.

Expression, Purification, And Activity Of Peptidyl-Trna Hydrolase 1 Of Rickettsia Rickettsii, Jessica Osler

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

One-Pot Silyl Ketene Acetal-Formation-Mukaiyama–Mannich Additions To Imines Mediated By Trimethylsilyl Trifluoromethanesulfonate, C. Wade Downey, Jared A. Ingersoll, Hadleigh M. Glist, Carolyn M. Dombrowski, Adam T. Barnett

Chemistry Faculty Publications

In the presence of trimethylsilyl trifluoromethanesulfonate and trialkylamine base, thioesters are readily converted to silyl ketene acetals in situ and undergo Mukaiyama–Mannich addition to N-phenylimines in one pot. The silyl triflates appears to play two roles, activating both the thioester and the imine. This process also works well when thioesters are replaced with amides, esters, or ketones. Products are isolated as desilylated anilines without the necessity of a deprotection step. Yields range from 65-99%.

Spectroscopic Characterization Of Lanthanum-Mediated Hydrocarbon Activation, Dilrukshi C. Hewage

Theses and Dissertations--Chemistry

Lanthanum (La)-promoted hydrocarbon activation reactions were carried out in a laser vaporization metal cluster beam source. Reaction products were identified by time-of-flight mass spectrometry, and the approximate ionization thresholds of La-hydrocarbon complexes were located with photoionization efficiency spectroscopy. The accurate ionization energies and vibrational frequencies of the La complexes were measured using mass analyzed threshold ionization (MATI) spectroscopy. Their molecular structures and electronic states were investigated by combing the MATI spectroscopic measurements with quantum chemical and Franck-Condon factor calculations.

In this dissertation, La-mediated C-H and C-C bond activation reactions were investigated for several small alkynes (acetylene, propyne) and alkenes (propene, …

Unhindered Triangulene Salt Pairs: Substitution-Dependent Contact Ion Pairing And Complex Solvent-Separated Discotic Ions In Solution, Subrahmanyam Modekrutti

Theses and Dissertations--Chemistry

This work sought to enforce aromatic interactions between compatible π-molecular orbital systems with ionic bonding. In this case the interacting partners are oppositely charged discotic triangulene derivatives. The observed properties of the heterodimeric ion-pairs likely arise due to a hypothetical synergy between electrostatics and π-interactions. The work presented here describes investigation of putative covalency arising from this hypothetical synergy in the electrostatics driven π-stacking. In order to probe this, various hypotheses were made and experiments were designed to test their validity. The results from the experiments show existence of contact ion-pairs and complex solvent-separated discotic ions in solution. The formation …

Long-Term Litter Decomposition Controlled By Manganese Redox Cycling, Marco Keiluweit, Peter Nico, Mark E. Harmon, Jingdong Mao, Jennifer Pett-Ridge, Markus Kleber

Chemistry & Biochemistry Faculty Publications

Litter decomposition is a keystone ecosystem process impacting nutrient cycling and productivity, soil properties, and the terrestrial carbon (C) balance, but the factors regulating decomposition rate are still poorly understood. Traditional models assume that the rate is controlled by litter quality, relying on parameters such as lignin content as predictors. However, a strong correlation has been observed between the manganese (Mn) content of litter and decomposition rates across a variety of forest ecosystems. Here, we show that long-term litter decomposition in forest ecosystems is tightly coupled to Mn redox cycling. Over 7 years of litter decomposition, microbial transformation of litter …

Light Controlled Drug Activation And Release, Jonathon Sheldon

Theses and Dissertations

Cancer constitutes a terrible burden on modern society. In the United States there are an estimated 1,658,370 new cancer diagnoses resulting in 589,430 deaths in 2015 alone.^[1] An estimated 41,170 of these cases will be diagnosed right here in Virginia. With new cancer patients comes the expanding demand for new treatments. As we all know, many modern chemotherapeutics cause adverse reactions to patients. This is because the toxic nature of these therapies often affects normal tissue alongside the tumors that are infesting the body. Therefore, researching novel ways to make chemotherapeutics selective for cancer, while leaving healthy tissue unscathed, …

Gas-Phase Reactions And Mechanistic Details Of Gold, Silver, And Iridium Complexes, Christopher Swift

Theses and Dissertations

The ever increasing demand for more efficient and environmentally benign routes for synthesizing target compounds, has led to the use of organometallic catalysts. This demand has created the need to understand the mechanistic details that are at work in these organometallic catalytic cycles. Along with this, there is a demand for new organometallic catalysts that are tailored for specific transformations. This presents a myriad of challenges for organometallic chemists. Unfortunately, it is often difficult to gain an understanding of the reaction mechanisms at work when the intermediates are too short lived to be observed in the condensed phase. It is …

Synthesis Of Unnatural Amino Acids For Genetic Encoding By The Pyrrolysyl-Trna/Rna Synthetase System, William A. Knight

Theses and Dissertations

The complexity of all biomolecules in existence today can be attributed to the variation of the amino acid repertoire. In nature, 20 canonical amino acids are translated to form these biomolecules, however, many of these amino acids have revealed posttranslational modifications (i.e. acetylation, methylation) after incorporation. Amino acids that exhibit PTM are known for their involvement in cellular processes such as DNA repair and DNA replication; these PTMs are commonly found on histones within the chromatin complex. Utilization of in vivo site-specific incorporation has recently reported functionality of post-translationally modified amino acids.1 xii Here we report the synthesis and in …

A Continuous Process Towards The Synthesis Of Quinolones, Stevara N. Clinton

Theses and Dissertations

Abstract

The development of quinolones is described from the first quinolone to the latest fluoroquinolones. Quinolones have generated considerable interest since their discovery because of their antibacterial capabilities. Analogs incorporating the 4-quinolone ring system comprise a largely expanding group of synthetic compounds. The development of antibacterial resistance has created the need for an efficient synthesis of quinolones that can be easily adapted toward the assembly of quinolone based antibacterial drugs.

There are several reported approaches to the 4-quinolone ring system. Many of these methods use expensive starting materials, require the removal of high boiling solvents, or use high temperature conditions …

Diazaborole Linked Porous Polymers: Design, Synthesis, And Application To Gas Storage And Separation, Zafer Kahveci

Theses and Dissertations

The synthesis of highly porous organic polymers with predefined porosity has attracted considerable attention due to their potential in a wide range of applications. Porous organic polymers (POPs) offer novel properties such as permanent porosity, adjustable chemical nature, and noteworthy thermal and chemical stability. These remarkable properties of the POPs make them promising candidates for use in gas separation and storage. The emission of carbon dioxide (CO₂) from fossil fuel combustion is a major cause of global warming. Finding an efficient separation and/or storage material is essential for creating a cleaner environment. Therefore, the importance of the POPs …