Organic Chemistry Commons^™

Green Synthesis Of Glutethimide Intermediate Via Nash Reaction, Zahria Patrick

Undergraduate Research Symposium

The purpose of my research project is to utilize green chemistry principles to synthesize an intermediate for Glutethimide, a drug used to treat patients with insomnia. Many pharmaceutical processes require the use of halide-containing chemicals which are harmful to the environment when discarded as waste. Not only does this waste affect the quality of drinking water and aquatic life, but it affects the economy as well. The cost of waste disposal increases with the increasing difficulty of treating it and thus raises the cost of production for pharmaceutical companies.
The reaction of choice is a nucleophilic aromatic substitution of hydrogen, …

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon

Electronic Theses and Dissertations

This thesis describes the isolation, structure elucidation, and synthesis of natural products from marine cyanobacteria. A crude extract from a cyanobacterium collected in Curacao showed selective affinity for the dopamine D₅ receptor in a screen against a panel of CNS receptors. Due to the high similarity of the D₅ and D₁ receptor, to date there are no known ligands that differentiate them. Attempts to purify the compound responsible for this affinity led to the isolation of the known compound caylobolide A. A second extract from a cyanobacterium collected in Panama underwent bioassay-guided fractionation and yielded the novel …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

Silver-Catalyzed Synthesis Of Disubstituted Fluorinated Isoxazoles, Micah Stewart

Honors Theses

The presence of fluorine can provide organic compounds with useful biological properties, such as increased metabolic stability and drug uptake. Because of these advantages, fluorinated compounds make up about 30% of the drug industry. However, fluorination of complex molecules is difficult due to fluorine’s high electronegativity.

Fluorinated isoxazoles are of particular interest in the pharmaceutical industry. Isoxazoles are five-membered heterocycles with oxygen and nitrogen in the 1, 2 positions that are able to engage in interactions unavailable to other ring structures, conferring advantageous biological properties upon compounds containing them. However, there are limited synthetic routes for fluorinated isoxazoles, and those …

“Treat Me Covalently” – New Tools To Improve Covalent Drug Design For Advancement Of Cancer Treatments, Yuliya Mazo

Student Theses and Dissertations

The goal of this project was to investigate the complex mechanism of covalent bonding among different molecules and their targets in a modeling software ICM-Pro. Specifically, it included the identification of fundamental aspects of a covalent bonding mechanism of the Michael addition reaction. Michael addition reaction of electrophilic α, β-unsaturated carbonyl compounds with a nucleophilic cysteine residue in thymidylate synthase, papain, and EGFR tyrosine kinase were examined. Thymidylate synthase and EGFR were chosen because they are important targets in the treatment of various types of cancer. In order to find the most optimal parameters, identification and assessment of the effect …

Diastereoselective Synthesis Of 2,4,6-Trisubstituted Piperidines Via Aza-Prins Cyclization, John A. Hood

Honors Theses

The nitrogen heterocycles are shared amongst 59% of Food and Drug Administration (FDA) approved small molecule pharmaceuticals with the six-membered piperidine representing the most common moiety. Given the versatility and potential to yield derivatives with broad biological activities, the discovery of new chemical methods to generate these heterocycles in a more time and cost-efficient manner is desired. While there are existing racemic methods to access this class of molecule, the objective of this research is to pioneer a new novel six-step method to generate 2,4,6-trisubstituted piperidines with stereoselective control.

The first step is a condensation between a nonenolizable aldehyde and …

Modification Of 4,5- Aminoglycosides To Overcome Drug Resistance Bacteria And Toxic Side Effect, Guanyu Yang

Wayne State University Dissertations

ABSTRACT

MODIFICATION OF 4,5- AMINOGLYCOSIDES TO OVERCOME DRUG RESISTANCE BACTERIA AND TOXIC SIDE EFFECT

by

Guanyu Yang

September 2018

Advisor: Professor David Crich

Major: Chemistry

Degree: Doctor of Philosophy

Infectious diseases causing by antibiotic resistant pathogen are one of the major threat to human health and society today. Many researchers tried to develop next generation of antibiotics by reinvesting the existing antibacterial drugs. Aminoglycosides have long been used as highly potent and broad-spectrum antibiotics for treating bacterial infections. But their side effect, especially the irreversible ototoxicity, and the fast-growing resistant problem limit their application. The goal of this research was …

Characterization Of 3-Ester And 3-Carbamate Derivatives Of N-Acetyl-D-Glucosamine And Their Use In Controlled Drug Delivery, Consuelo Garcia

Chemistry & Biochemistry Theses & Dissertations

Low molecular weight gelators (LMWGs) are a class of compounds which reversibly form a network that traps solvents to form gels. Gelation by LMWGs is driven solely by non-covalent interactions such as hydrogen bonding, π - π stacking, and hydrophobic interactions. LMWGs can be designed such that the gel-sol and sol-gel transitions happen as a response to a specific stimulus. These stimulus responsive gels or “smart” gels can be used in a wide variety of applications including tissue regeneration, biosensing, and controlled drug delivery.

Among the different types of compounds that are LMWGs, carbohydrate based systems are especially interesting. Carbohydrates …

Synthesis And Biological Activity Of Novel Quorum Sensing Compounds, Joseph Nicholas Capilato

Theses and Dissertations

Bacteria communicate with chemical signals in a process known as quorum sensing. This population density-dependent process involves the bacterial production, release and detection of structurally specific small molecules and enables the bacterial pathogen to regulate its virulence on a population-wide level. Using a variety of chemical and biological techniques, I have studied various quorum sensing systems in several bacteria, including Vibrio cholera and Pseudomonas aeruginosa. A key principle of this research involves the design, synthesis and testing of novel compounds for their biological activity. These molecules are typically based off of an initial lead target, which is often identified …

Catalytic Transfer Hydrogenation Of Nitroalkenes To Primary Amines, Brendan Phillips

Chemistry Honors Papers

This work describes synthetic methodology development in organic chemistry. The goal of this work is to demonstrate new ways of making biologically-relevant molecules that are in line with the principles of green chemistry (chemical practices which seek to be, regarding human and environmental health, benign by design). To this end, a new method has been developed toward the introduction of primary amine functionalities into organic molecules from readily-available aldehydes, via reduction of nitroalkene intermediates. Traditional methods of reducing nitroalkenes to primary amines require harsh conditions, often produce stoichiometric amounts of metal salt waste, and present significant safety challenges to the …

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 …

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. …