Chemistry Commons^™

Synthesis Of Chiral Amino Acids Via Direct Amination Of Diazo Ester With A Rhodium-Based Catalyst, Steven J. Boyles

Honors College Theses

Amino acids are critical molecules within living organisms as they are the building blocks of proteins. In organisms, proteins serve as regulators of necessary processes, structural components in tissue, hormones, and neurotransmitters. Amino acid therapy is an emerging treatment in the medical field used to treat symptoms of diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Amino acid therapies have also shown promising effects when it comes to treating mood disorders and weight management. In order to increase the number of amino acids available and increase the potential treatments for other ailments, there is a drive to increase …

Esipt-Enabled Alkyne Migration Provides Rapid Access To Benzoxazinones, Andrés G. Muñoz

Electronic Theses and Dissertations

Benozoxazinones have long been of interest to agrochemical scientists and medicinal chemists because of their widespread biological activity. These scaffolds are also of interest to synthetic chemists, who recognize the utility of benzoxazinones for accessing functionalized heterocycles. The use of efavirenz, a benzoxazinone-based reverse transcriptase inhibitor used in the treatment of HIV-1, has brought increased attention to this privileged pharmacophore. While there exist numerous strategies for synthesizing benzoxazinones, methods that do not require the use of acutely toxic and environmentally hazardous reagents are lacking. Consequently, there is a need to develop new methods for constructing this valuable scaffold. Herein, we …

Asymmetric Cuh-Catalyzed Reductive Coupling Of Alleneamides With Carbonyl Electrophiles And The Mechanistic Investigation Into The Suzuki-Miyaura Cross-Couplings Of Electron-Deficient Systems, Samantha L. Gargaro

Theses and Dissertations

Most natural products and other biologically active small molecules contain multiple stereogenic heteroatoms throughout their carbon scaffold. As a result, methods to install these multi-heteroatom functionalities efficiently are highly desirable. Reductive coupling reactions have been studied extensively, and reductive allylation has been a key method for generating chiral secondary and tertiary allylic alcohols. This work focuses on utilizing naturally abundant and inexpensive Cu for the asymmetric reductive coupling of alleneamides with carbonyl electrophiles to access highly functionalized multi-heteroatom scaffolds that are difficult to produce via traditional methods. Described herein are methods for these asymmetric reductive coupling reactions. Chapter 1 describes …

An Intramolecular Method For The Formation Of Glycosidic Bonds, Sudeera Nadeeshani Kamburugamuwa Kamburugamuwe Loku Acharige

Electronic Theses and Dissertations

The improved understanding of carbohydrate functions in biological systems has increased the demand for well-characterized and pure carbohydrates in biomedical research. Chemical synthesis is the most feasible method to satisfy the scientific demand despite the inherent challenges of the glycosylation reaction. Therefore, it is essential to investigate novel methods for the formation of glycosidic bonds. In this work, an intramolecular method was developed using a thio-methylene-silyl linker to tether a glycosyl donor and acceptor. The glycosylation conditions resulted in the formation of both anomeric isomers with a preference for the inversion pathway, which is inconsistent with an entirely intermolecular glycosylation …

Generation And Reactions Of Cyclopropyl Vinylidene Carbenes, Nguyen Nhat Thu Le

Honors Theses

This study aimed to generate cyclopropyl methyl vinylidene carbene and cyclopropyl phenyl vinylidene carbene via photochemical routes. The precursors to these two carbenes were synthesized from phenanthrene by a two-step procedure. However, these precursors could not be fully purified because the second step generated many side products with similar properties as the precursors. A crude sample of each precursor were photolyzed with UV light in the range of 315 to 400 nm. Vinylidene carbenes are known to rapidly rearrange into alkynes, so the formation of these cyclopropyl vinylidene carbenes was monitored through the formation of their rearrangement products, cyclopropyl methyl …

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 …

Synthesis Of New Bodipy Analogs, John Dilyard

Williams Honors College, Honors Research Projects

This report examines the synthesis of new ligands based upon dipyrazolylmethane and diindazolylmethane. The goal of these modifications is to increase the acidity of the proton on the methyl carbon to allow for deprotonation. The ligands synthesized were dipyrazolylphenylmethane and diindazolylphenylmethane, as well as modifications of the latter. The products were analyzed by NMR spectroscopy and one crystal structure was obtained of diindazolylphenylmethane.

Synthesis, Properties, And Solid-State Structures Of A Series Of 6,13-Dicyanoheteropentacene Analogues: Towards New Liquid Crystalline Materials, L Hiscock, Kenneth E. Maly, Louise N. Dawe

Theses and Dissertations (Comprehensive)

The focus of this thesis is the synthesis of novel heterocyclic pentacene analogs and the investigation of their self-organization for the development of new materials for organic electronics. The thesis consists of two interrelated projects: the first being development of an improved synthesis of a series of liquid crystalline dicyanotetraoxapentacenes (DCTOPs) while the second entails the exploratory synthesis of several novel dicyanoheteropentacene analogues and a preliminary investigation of their photophysical properties and solid-state structures. Both of these projects centre around the use of nucleophilic aromatic substitution reactions on tetrafluoroterephthalonitrile.

Soluble, tetrakis(bis(alkoxy)phenyl)-substituted DCTOPs were originally synthesised via a short synthesis complicated …

New Ventures In Amidine-Based Catalyst Design, Nicholas Alan Ahlemeyer

Arts & Sciences Electronic Theses and Dissertations

Two new cascade transformations of α,β-unsaturated thioesters catalyzed by amidine-based catalysts have been developed. First, a reagent-free transformation of o-formylaryl cinnamoyl thioesters catalyzed by HBTM-2 to produce 2-substituted thiochromenes achieved high enantioselectivities and yields while forming carbon dioxide as the only byproduct. Second, a highly diastereo- and enantioselective tandem rearrangement of less reactive enone thioesters into tricyclic thiochromanes in the presence of electron-rich amidine-based catalysts was developed. These catalysts were designed with the help of DFT calculations. H-PIP, the first chiral amidine-based catalyst synthesized in our group, performed the best overall in the thiochromane synthesis.

The second chapter of this …

Producing Dihydrofurans Using Palladium (Ii) Catalyst And Optimized Base, Chandler Mitchell

Undergraduate Honors Thesis Collection

Dihydrofurans serve as building blocks for other compounds in organic synthesis. The main goal of this project was to discover an efficient and relatively inexpensive pathway for producing monosubstituted dihydrofurans in high yield from cyclic boronic half acids. Aldehydes were converted to homoallylic alcohols by the addition of allylmagnesium bromide. The alcohols were then transformed into cyclic boronic half acids using ringclosing metathesis with Grubbs 1st Generation Catalyst and alkenyl boronic esters. Finally, monosubstituted dihydrofurans were produced using a palladium (II) catalyst with a base. Palladium (II) catalysts that were tested include [1,1'- bis(diphenylphosphino)ferrocene]palladium (II) dichloride, palladium (II) acetate with …

A Novel Synthesis And Subsequent Decyclization Of Iminothiozolidinones: Expansion Of Thiourea Chemistry For Biological Applications, Constance D. Franklin

Theses and Dissertations

Small molecule synthesis has become a valuable tool in the study of biological systems. Biologically active compounds can be designed based on well-characterized endogenous systems or they can be found through the screening of large libraries of small molecules. This work involves the development of a small library of cyclic thiourea-based small molecules by use of an unreported synthetic pathway. Briefly, parent thioureas were cyclized by reaction with bromoacetyl bromide, and one or two isomeric heterocycles were found to form. Further studies indicated that the reaction could be easily manipulated by temperature or solvent to effectively control the product distribution. …

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 …

Microfluidic Syntheses Of Pet Radiotracers Via Fluorodenitration, Thomas Madison Moore

Doctoral Dissertations

This research study is focused on the syntheses of radiotracers for use in positron emission tomography [PET] via fluorodenitration and fluorodehalogenation under microfluidic conditions. Methodology has been developed for radiolabeling via fluorodenitration under microfluidic conditions and comparisons made to dehalogenation reactions. Developmental work was carried out on commercially available compounds containing a variety of functional groups. Subsequent production of radiotracers has been performed with precursors provided by collaborators as well as those synthesized in our laboratory.

The Application Of Novel Donor Acceptor Cyclopropanes In The Synthesis Of Linearly Fused Tricyclic Triazoles, Michelle E. Flisar

Electronic Thesis and Dissertation Repository

Previous work in the Kerr group has shown the success of donor-acceptor cyclopropanes as substrates in a variety of synthetic reactions; this document will apply the use of donor acceptor cyclopropanes in various synthetic reactions. This was done using a 2-substituted 1,1-cyclopropanediester, in the Overman Rearrangement, which has yet to be explored using DA cyclopropanes. Another useful DA cyclopropane is the novel acetylene-bearing donor acceptor diester cyclopropanes which would be synthetically useful in a wide variety of reactions. In particular, the Conia-ene cyclization occurred intramolecularly with this alkyne DA cyclopropane with a large library of nucleophiles. Finally, taking this acetylene-bearing …