Organic Chemistry Commons^™

Synthesis Of Novel Aporphine-Inspired Neuroreceptor Ligands, Nirav R. Kapadia

Dissertations, Theses, and Capstone Projects

Aporphines are a group of tetracyclic alkaloids that belong to the ubiquitous tetrahydroisoquinoline family. The aporphine template is known to be associated with a range of biological activities. Aporphines have been explored as antioxidants, anti-tuberculosis, antimicrobial and anticancer agents. Within the Central Nervous Systems (CNS), aporphine alkaloids are known to possess high affinity for several clinically valuable targets including dopamine receptors (predominantly D₁ and D₂), serotonin receptors (5-HT_1A and 5-HT₇) and α adrenergic receptors. Aporphines are also inhibitors of the acetylcholinesterase enzyme – a clinical target for the treatment of Alzheimer’s disease. Considering the …

Rapid Access To Conformationally-Constrained Oxatricycles Via Ugi-Smiles Couplings, Bree Richey, Katelynn M. Mason, Michael S. Meyers, Sarah Luesse

SIUE Faculty Research, Scholarship, and Creative Activity

Use of allylamine and substituted 2-furaldehydes as components in Ugi-Smiles couplings of 2-nitrophenol provide ready access to N-aryl epoxyisoindolines. These adducts form via a dual event involving the Ugi-Smiles multicomponent reaction and an intramolecular Diels-Alder cycloaddition with the furan ring.

Kdac8 With High Basal Velocity Is Not Activated By N-Acetylthioureas, Tasha B. Toro, Subramanya Pingali, Thao P. Nguyen, Destane S. Garrett, Kyra A. Dodson, Kyara A. Nichols, Rashad A. Haynes, Florastina Payton-Stewart, Terry J. Watt

Faculty and Staff Publications

Lysine deacetylases (KDACs) are enzymes that reverse the post-translational modification of lysine acetylation. Recently, a series of N-acetylthioureas were synthesized and reported to enhance the activity of KDAC8 with a fluorogenic substrate. To determine if the activation was general, we synthesized three of the most potent N-acetylthioureas and measured their effect with peptide substrates and the fluorogenic substrate under multiple reaction conditions and utilizing two enzyme purification approaches. No activation was observed for any of the three N-acetylthioureas under any assayed conditions. Further characteriza- tion of KDAC8 kinetics with the fluorogenic substrate yielded a k cat /K M of 164 …

Quinolines: Novel Synthesis And Derivatives Of Heterocyclic Bioactive Agents, Ginelle A. Ramann

Electronic Theses and Dissertations

Tuberculosis is a pulmonary disease that has ravaged the world throughout history. Even today, many developed and developing countries are experiencing this plight, made worse by the scourge of antibiotic-resistant bacteria.

Mycobacterium tuberculosis's class II fructose-1,6-bisphosphate aldolase presents an interesting target in the design of new therapies against this disease. Previous attempts to construct an inhibitor to this enzyme fell short due to poor selectivity or poor cellular uptake. However a new class of noncompetitive inhibitor based on 8-hydoxyquinoline-2-carboxylic acid presents a fresh approach. Preliminary studies indicate various modifications to this scaffold could be beneficial to its inhibitory efficacy.

Modifications …

A Bond Length – Bond Valence Relationship For Carbon – Nitrogen Bonds, C. Harris, F. D. Hardcastle

Journal of the Arkansas Academy of Science

In a recent study, Pauling’s relationship between bond length and valence was derived along with a definition for his fitting parameter b that incorporates the orbital exponents for each atom contributing to the bond of interest. The values of b for various bonds, including C-N bonds, were calculated using the orbital exponent data. In this study, Pauling’s correlation between bond length and bond valence, as well as his valence sum rule, were used with the recently-derived definition for b in order to produce a relationship specifically applicable to C-N bonds. The resulting equation was checked against published x-ray diffraction data …

Photoassisted Generation Of Complex N, O, S Polyheterocycles, Weston James Umstead

Electronic Theses and Dissertations

This research set out to continue the exploration and diversification of excited state o-azaxylylene cycloadditions, utilizing both pre-photochemical and post-photochemical modifications.

Pre-photochemical modifications came through the addition of heteroatoms, namely nitrogen and oxygen, to the tether that links the unsaturated photopendant to the photogenerated o-azaxylylene. Photochemistry resulted in the formation of new, interesting N, O, S polyheterocycles.

Post-photochemical modifications took place through several different cycloaddition reactions, including a [4+2] hetero-Diels Alder reaction, a [4+2] Povarov cyclization, a [3+2] nitrile oxide addition, and a [3+2] nitrone cyclization. These reactions were applied first to a model system, and then to …

Studying The Atp Cosubstrate Promiscuity Of Nucleotide And Lipid Kinases, Thilani Murium Anthony

Wayne State University Dissertations

The kinase family consist of a large assortment of enzymes that phosphorylate a variety of substrates, including proteins, nucleosides, polynucleotides, lipids, sugars, and other small molecules. The Pflum lab recently found that protein kinases promiscuously accept an ATP analog containing a biotin at the γ-phosphate (ATP-biotin) as a cosubstrate to label the hydroxyl side chains of Ser, Thr and Tyr residues with biotin. The main goal of this new project is to extend the use of kinase-catalyzed biotinylation towards polynucleotides. Crystallographic studies of T4 polynucleotide kinase (T4 PNK) that phosphorylates the 5’-hydroxyl termini of DNA and RNA show a solvent …

Development Of Gamma-Modified Atp Analogs To Study Kinase-Catalyzed Phosphorylations, Ahmed Eid Fouda

Wayne State University Dissertations

Kinase-catalyzed protein phosphorylation is one of the most important post-translational modifications that controls cascades of biochemical reactions. Irregularities in phosphorylation result in many diseases, such as diabetes mellitus, Parkinsons, and cancer. The development of new methods to monitor kinase-catalyzed phosphorylation is needed to decipher details of normal and diseased cell signaling. The Pflum lab recently developed several -modified ATP analogs to study kinase catalyzed phosphorylation reactions. The -modified ATP analogs have different tags, such as biotin for substrate labeling or aryl-azide for kinase substrates identification. Unfortunately, use of -modified ATP analogs was limited to in vitro studies due to the …

Synthesis Of Apramycin And Paromomycin Derivatives As Potential Next Generation Aminoglycoside Antibiotics And Chemistry Of Isothiocyanato Sialyl Donors, Appi Reddy Mandhapati

Wayne State University Dissertations

AGAs are clinically important antibacterials for human therapy and have long been used as highly potent antibiotics for treating several bacterial infections. The fidelity of protein synthesis is affected by AGAs in the course of binding to specific sites of the bacterial rRNA. The clinical use of AGAs and their applications as therapeutics is restricted by toxicity (irreversible ototoxicity and reversible nephrotoxicity) and by the resistance of pathogens. The objective of this research was the development of proficient AGAs that are less toxic (i.e., more selective) and that evade resistance. The first three chapters of this thesis are aimed towards …

Substrate Specificity Of The Lipn Hydrolase From Mycobacterium Ulcerans, Stephanie Raynor

Undergraduate Honors Thesis Collection

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a tropical skin disease that affects thousands of individuals annually. Recent studies have revealed that lipolytic enzymes are involved in the pathogenicity processes of mycobacterium and could be potential targets for novel antibiotics. LipN is one proposed serine hydrolase in Mycobacterium ulcerans that contains the conserved α/β hydrolase protein fold and utilizes the conserved catalytic traid of serine, histidine, and aspartate/glutamate. The physiological substrate and biological role of LipN from M. ulcerans have not yet been determined. In this study, LipN was cloned into a pET28a plasmid and overexpressed in an …

Phenanthrene...With A Twist!, Nicholas S. Kim

Honors Theses

The twisted and sterically hindered 4,5-dibromophenanthrene, was synthesized from 2,6-dibromoiodobenzene in a four-step pathway, or from 1,3-dibromobenzene in a three-step pathway. Then, 4,5-dibromophenanthrene was subjected to a Kumada coupling, leading to the synthesis of an even more twisted 4-bromo-5-tert-butylphenanthrene. Computational studies using density functional theory were performed to compare experimental and theoretical characteristics of these compounds, such as dihedral angles, optimized structures, and transition state energy barriers.

The purpose of these experiments is to fill gaps in chemical databases, synthesize more pronounced twists in normally planar phenanthrene molecules, and to ultimately synthesize 4,5-bis-tert-butylphenanthrene, which may have …

Part I: Photochemical Generation Of Cyclohexyne From A Hydrocarbon Precursor Part Ii: A Triptycenyl Flower, Daniel Maurer

Honors Theses

Part I

Photolysis of phenanthrene-based methylenecyclopropane derivatives have previously been shown to generate alkylidenecarbenes, which readily rearrange to form alkynes. In this work, we show that photolysis of an analogous cyclic alkylidenecarbene precursor at ambi- ent temperature forms cyclohexyne via the putative cyclopentylidenecarbene, and can be trapped by dienes via a Diels-Alder reaction. Cyclohexyne and other strained cycloalkynes are of much interest to theoreticians and experimentalists alike. Results of coupled-cluster and DFT calculations on the potential energy surface of cyclopentylidenecarbene and the corresponding strained cyclohexyne are also presented. The photochemical generation of cy- clopentylidenecarbene, and thus cyclohexyne, from a hydrocarbon …

Experimental And Computational Study Of Methylphenylvinylidene And Its Rearrangements, Xi Yang

Honors Theses

In this study, the synthesis and properties were explored of the compound methylphenylvinylidene (MPV), a vinylidene carbene with methyl and phenyl groups as substituents. A phenanthrene-based precursor, 1-(1-phenylethylidene)-1a,9b-dihydro-1H-cyclopropa[l]phenanthrene, was synthesized in three steps and was subjected to photolysis in C₆D₆ at ambient temperature. During photolysis, the MPV carbene rearranged into 1-phenylpropyne via a 1,2-phenyl shift, instead of 1,2-methyl shift, confirmed by photolysis of ¹³C-labeled precursor. This experimental result is consistent with computational results using the CCSD(T)/cc-pVTZ//B3LYP/6-31+G* method. The calculations suggest that the 1,2-phenyl shift in singlet carbene requires 3.8 kcal/mol to overcome …

Quantitative Model For Rationalizing Solvent Effect In Noncovalent Ch-Aryl Interactions, Bright C. Emenike, Sara N. Bey, Brianna C. Bigelow, Srinivas V.S. Chakravartula

Publications and Research

The strength of CH–aryl interactions (ΔG) in 14 solvents was determined via the conformational analysis of a molecular torsion balance. The molecular balance adopted folded and unfolded conformers in which the ratio of the conformers in solution provided a quantitative measure of ΔG as a function of solvation. While a single empirical solvent parameter based on solvent polarity failed to explain solvent effect in the molecular balance, it is shown that these ΔG values can be correlated through a multiparameter linear solvation energy relationship (LSER) using the equation introduced by Kamlet and Taft. The resulting LSER …

Solvent Free Vanadium Mediated Organic Transformations, Garrett Oberst

Undergraduate Honors Thesis Collection

A mixture of vanadium(V) oxide and copper sulfate was used to catalyze oxidative transformations in a variety of organic compounds. Multiple functionalities were tested, including thiols, amines and alcohols. Various transformations were observed resulting in various oxidized products, including coupling reactions. Reactions were performed in a solvent-free environment due to the insoluble nature of vanadium(V) oxide in common organic solvents. Results were analyzed using HNMR and GCMS.

Synthetic Study Toward Lycopodium Alkaloids Via A Common Bicyclic Intermediate, Michaela Cara Vertorano

Legacy Theses & Dissertations (2009 - 2024)

The lycopodium alkaloids are a family of over 270 naturally occurring compounds, many of which are bioactive. Therefore, developing an efficient manner by which these alkaloids can be synthesized could be incredibly useful in studying their potential medicinal benefits. Herein, steps toward this goal were accomplished. A bicyclic ring structure was synthesized in few steps from commercially available starting materials. This structure can be viewed as a key intermediate from which several lycopodium alkaloids could be synthesized in relatively few steps. The ring system was subject to an aza-Prins cyclization reaction to synthesize the alkaloids lycopodine. Unfortunately the current synthetic …

The Chemistry Of New Garlic-Derived Organosulfur Compounds And The Molecular Basis Of Olfaction, Berenice Dethier

Legacy Theses & Dissertations (2009 - 2024)

Garlic is a very popular condiment that has been used around the world for centuries. It is also a source of a remarkably extensive range of organosulfur compounds, whose chemistry is the focus of this thesis. The central reaction in formation of these compounds is the enzymatic cleavage of alk(en)yl cysteine sulfoxides by alliinases, which leads to sulfenic acids. The latter can then undergo condensation and rearrangement into various organosulfur compounds. Three aspects of the chemistry of garlic have been investigated in this thesis.

The Danger Of Scented Candles, Shahad Alsayyad

Natural Sciences Student Research Presentations

These slides, presented at the Natural Sciences Poster Session at Parkland College, show how scented candles release organic compounds whether lit or not, can cause diseases, and indoor air pollution.

Decoding The Double Helix: Frederick Sanger And Sanger Sequencing, Creighton A. Jackson

Natural Sciences Student Research Presentations

This is a poster presented at the Natural Sciences Poster Session at Parkland College, which summarizes the work of Frederick Sanger, a British biochemist and the only recipient of two separate Nobel Prizes in the field of chemistry. His first prize was awarded for his work deciphering the structure of the protein insulin. This discovery would go on to influence research on proteins and DNA as it determined that proteins had definite structures and led to the theory that DNA directed the construction of proteins. His second was awarded for this work on the Sanger method of DNA sequencing and …

Facile Synthesis Of Tertiary Aliphatic Amine– Containing Cyclic Motif Via Neutral Aminyl Radical Cyclization, Heng Chen

Wayne State University Theses

Tertiary amine–containing cyclic motifs are prevalent in natural products and pharmaceutical lead targets. Inspired by these biological active molecules, one focus in our lab is the development of neutral aminyl radical chemistry in the synthesis of tertiary aliphatic amine–containing cyclic compounds. In this project, I investigated the mono- and tandem cyclization of aminyl radical with different types of olefins (terminal olefin, enone, and styrenyl). The effect of the hydrogen atom donor and the limitation of the reaction will be discussed.