Organic Chemistry Commons^™

Synthetic And Biological Studies On Benzazepine Derivatives As Dopamine Receptor Ligands, Rajan Giri

Dissertations, Theses, and Capstone Projects

Dopamine (DA) receptors, members of the G-protein coupled receptors (GPCRs) family, are divided in two groups based on their transmembrane structural homology domains: D1R-like (D1R, D5R sub-types) and D2R-like DA receptors (D2R, D3R and D4R sub-types). Disturbances in dopaminergic neurotransmission are associated with several CNS disorders. Hence, DA receptor selective ligands have been sought as pharmacological agents to normalize perturbations in the dopaminergic system. Despite several notable efforts, the discovery of highly selective ligands for dopamine receptor sub-types has proved challenging due to close transmembrane structural similarity, especially between DA receptor sub-types within the same group.

The 1-phenylbenzazepine scaffold is …

Iron And Iodine-Mediated Reactions, Xiaochen Liu

Dissertations, Theses, and Capstone Projects

This thesis work focuses on developing facile, low-cost, and environmentally friendly reactions, specifically the iron and iodine-mediated reactions, including (1) iron-catalyzed reductive ring-opening of 3,5-disubstituted isoxazoles and isoxazolines in aged N-methyl-2-pyrrolidone (NMP*), (2) iodine-mediated C-N bond cross-coupling reactions between amides and aldehydes, and (3) ICl-mediated functionalization of β-alkoxy alkynes – synthesis of α-iodo-γ-chloro-ketones.

Chapter I provides a background introduction on previous synthesis and applications of β-enaminones and 1,3-diketones that play as synthons or ligands. Ring-openings of heterocycles, such as isoxazoles and isoxazolines have attracted great attentions. A newly developed iron-catalyzed reductive system was established upon our previous palladium-catalyzed research. …

Photosensitization And Analytical Study On Reactive Oxygen Intermediates: Self-Sorting Surface Radicals And “On-Off” Sensitizer Function Mechanisms, Sarah J. Belh

Dissertations, Theses, and Capstone Projects

This thesis consists of four chapters which are detailed below. Chapter 1 is an introductory chapter, which lays out the background and purpose of the research.

Chapter 2 describes a study of the mobility of alkoxy radicals on a surface by detection of their recombination product. A novel method called symmetrical product recombination (SRP) utilizes an unsymmetrical peroxide that upon sensitized homolysis recombines to a symmetrical product [R'OOR → R'O•↑ + •OR → ROOR]. This allows for self-sorting of the radical to enhance the recombination path to a symmetrical product, which has been used to deduce surface migratory aptitude. SPR …

Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins, Eskil Me Andersen

Dissertations, Theses, and Capstone Projects

To create an efficient de novo photosynthetic protein it is important to create long lived charge separated states. Achieving stable charge separation leads to an increase in the efficiency of the photosynthetic reaction which in turn leads to higher yields of end products, such as biofuels, electrical charge, or synthetic chemicals. In an attempt to create charge separated states in de novo proteins we hypothesized that we could engineer the free energy gaps in the proteins from excited primary donor (PD) to acceptor (A), and A back to ground state PD such that the forward electron transfer (ET) would be …

Mechanism Of Action Of Dihydropteridine Reductase, Gabriela Arias De La Rosa

Dissertations, Theses, and Capstone Projects

Human dihydropteridine reductase is an enzyme that transfers a hydride from NADH to reduce quinonoid 7,8-dihydropterin (qBH₂) to 5,6,7,8-tetrahydropterin (BH₄), which is a cofactor important in the production of neurotransmitters.DHPR deficiency causes a drastic form of the neurological genetic disease phenylketonuria (PKU) that does not benefit from a phenylalanine-free diet.From site-directed mutagenesis studies, mostly on Rat DHPR, we know that certain residues are important for cofactor binding, substrate binding, and hydride transfer; however, there are still some questions about how DHPR works, particularly, because there is not a crystal structure of the tertiary complex: What is …

Interactions Of Organic Fluorophores With Plasmonic Surface Lattice Resonances, Robert J. Collison

Dissertations, Theses, and Capstone Projects

It is common knowledge that metals, alloys and pure elements alike, are lustrous and reflective, the more so when a metal surface is flat, polished, and free from oxidation and surface fouling. However, some metals reflect visible light, in the 380 nm to 740 nm range of wavelengths, much more strongly than others. In particular, some metals reflect wavelengths in certain portions of the ultraviolet (UV), visible, and near-infrared (NIR) regime, let us say 200 nm to 2000 nm, while absorbing light strongly in other segments of this range. There are several factors that account for this difference between various …

Asymmetric Alpha-Stannylation Of Heterocycles And Their Subsequent Use In Cross-Coupling Reactions, Haoran Zhao

Dissertations, Theses, and Capstone Projects

α-Substituted oxygen-containing heterocycles are commonly present in biologically active molecules. Statistics shows that at least one α-substituted ether moiety appears in over 20% of the top 200 small-molecule pharmaceuticals. This project illustrates a reliable regioselective method to introduce simple cyclic ethers towards the diversification of small molecules. Aryl halides bearing various functional groups were well tolerated independent of their electronic properties. It was found that cyclohexyl spectator ligands on tin selectively slows transmetallation of undesired units, circumventing the competitive transfer of n-butyl group from ⁿBu₃SnR reagents. Compared to the normally used ⁿBu₃SnR reagents, Cy …

I. Selective Chlorination And Fluorination Of Quinols Ii. Synthetic Study Of Strongylophorine-26, Sihan Li

Dissertations, Theses, and Capstone Projects

Organic compounds containing halogen are an important and useful class of intermediates that can be converted to other functionalities. This thesis describes our strategy in selective chlorination and fluorination of quinols to offer the corresponding aromatic structures. Quinols, or cyclohexadienones, as oxidized derivatives of phenols, have their remarkable chemical reactivities, including additions to enone, enolate alkylations, aldol reactions, cycloadditions, and rearrangements. Dienone-phenol rearrangement provides the asymmetric route since the stereocenters located in the six-membered ring of various cyclohexadienone were widely using in building larger chiral arrays for many total syntheses

Chapter one of this thesis discusses our new selective nucleophilic …

Small Molecule Synthetic Carbohydrate Receptors, Marcelo F. Bravo Carranco

Dissertations, Theses, and Capstone Projects

Carbohydrate – receptor interactions are often involved in the attachment of viruses to host cells, and this docking is a necessary step in the virus life cycle that precedes infection and, ultimately, replication. Despite the conserved structures of the glycans involved in docking, they are still considered “undruggable”, meaning these glycans are beyond the scope of conventional pharmacological strategies. Recent advances in the development of synthetic carbohydrate receptors (SCRs) – small molecules that bind carbohydrates – could bring carbohydrate-receptor interactions within the purview of druggable targets. Here we discuss the role of carbohydrate-receptor interactions in viral infection, the evolution of …

Synthesis And Antitumor Activity Of Potentially Tumor Targeting Analogues Of The Tetrahydrofuran Containing Acetogenins, Patricia Gonzalez Periche

Dissertations, Theses, and Capstone Projects

The tetrahydrofuran containing acetogenins (THF-ACGs) are a naturally occurring class of compounds with potent toxicity against a broad range of tumors, including multidrug resistant (MDR) strains. However, the equally high toxicity to normal cells presents a hurdle for their clinical advancement. This study entails synthetic and tumor targeting strategies that are relevant to their therapeutic development.

Chapter 1 presents a review of the synthesis and biological activity of the THF-ACGs. Chapter 2 covers a modular approach for the synthesis of libraries of THF-ACGs. This strategy is illustrated in the synthesis of C-10 epimers of 4-deoxyannonomontacin (4-DAN), one of the more …

A Brief Introduction To The Applications Of Small Organic Molecules As Food Additives, Zhou Zhou

Open Educational Resources

A new chapter in Introductory Organic Chemistry course. Lecture PowerPoint file and laboratory document are also included in this work.

• The goal of this chapter is to cover the basic ground of the food additives from the perspective of organic chemistry. This chapter has three parts.
  • Part one: Introduction of the food additive industry including the history, definition and the purposes of food additives.
  • Part two: The terminology in food additives and in organic chemistry, how to locate trustworthy data sheets for chemicals, and how to interpret the toxicity data.
  • Part three: Different families of organic compounds used as food …

Sugar-Derived Oleogels In Cosmetics And Food Applications: A Case Study Of Trehalose- And Mannitol-Based Gelators, Polina Tsupko

Dissertations and Theses

Gels represent an indispensable part of our everyday lives with direct applications in food, medicine, cosmetics and other industries. Amphiphilic molecules have been shown to act as low molecular weight gelators (LMWGs) and are becoming the main focus of several research groups. Their ability to self-assemble into various morphologies from micelles to bilayer sheets, and remain stable due to noncovalent forces responsible for the formation of the 3D network—Self-Assembled Fibrillar Network (SAFiNs)—is in the core of their ability to produce molecular gels. Those amphiphilic molecules capable of adsorbing at the interface and behaving as surface active agents are known as …

Reductions By Cobalt-Catalyzed Production Of Hydrogen Gas From Nabh4 In A Two-Chamber System, Joshua K. Mitchell

Dissertations and Theses

The work outlined in this thesis describes a bench-scale methodology involving a two-chamber system for conducting catalytic hydrogenation reactions by obtaining hydrogen (H₂) gas from stable sodium borohydride (NaBH₄). Whereas NaBH₄ is widely used for a variety of reductions and is known to produce H₂ gas in protic media, to our knowledge, there has been scant use of NaBH₄ in catalytic hydrogenation chemistry where it has been used as a source of H₂ gas. In this work, addition of a catalytic amount of CoCl₂•6H₂O as an aqueous solution …

“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 …

Microwave Solventless Synthesis Of Meso-Tetrakis (Pentafluorophenyl)Poprphyrin (Tppf20) And Tris(Pentafluorophenyl))Corrole [Chemistry], Sunaina Singh

Open Educational Resources

Organic chemistry is a two-semester course (Organic Chemistry I, SCC 251 and Organic Chemistry II, SCC 252) required for majors in Biology. The SCC 251 course has been designated for the Integrative Learning Core Competency as well the Digital Communication Ability. This course emphasizes the synthesis, structure, reactivity, and mechanisms of reaction of organic compounds. Laboratory stresses various organic synthetic and analytic techniques (distillation, extraction, chromatography and spectroscopy).

This lab provided an opportunity for students to go deeper with the chemistry content by correlating to the concepts they learned in General Chemistry courses such as Valence shell electron pair repulsion …

Synthesis And Evaluations Of “1,4-Triazolyl Combretacoumarins” And Desmethoxy Analogs, Tashrique A. Khandaker, Jessica D. Hess, Renato Aguilera, Graciela Andrei, Robert Snoeck, Dominique Schols, Padmanava Pradhan, Mahesh K. Lakshman

Publications and Research

1,4-Triazolyl combretacoumarins have been prepared by linking the trimethoxyarene unit of combretastatin A4 with coumarins, via a 1,2,3-triazole. For this, 4-azidocoumarins were accessed by a sequential two-step, one-pot reaction of 4-hydroxycoumarins with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), followed by reaction with NaN₃. In the reaction with BOP, a coumarin-derived phosphonium ion intermediate seems to form, leading to an O⁴-(benzotriazolyl)coumarin derivative. For the CuAAC reaction of azidocoumarins with 5-ethynyl-1,2,3-trimethoxybenzene, catalytic [(MeCN)₄Cu]PF₆ in CH₂Cl₂/MeOH with 2,6-lutidine, at 50 ^oC, was suitable. The 4-azidocoumarins were less reactive as compared to PhN₃ and …

Novel Heterocyclic Methodology For The Construction Of Natural Products, Robert C. Lapo

Dissertations, Theses, and Capstone Projects

The synthesis of heterocyclic compounds and their incorporation into total synthesis strategies are described. Three synthetic methodologies toward substituted indoles, isochromans, and fused multi-ring oxazolidinones have been examined. With the progress that has been made, further investigations will hopefully carry the concept to completion.

Chapter I is an introductory examination of the varied types and systematic nomenclature of heterocyclic structures, including common names. This continues on to their commercial and industrial usage, and their great importance in biological systems and natural product chemistry. Finally, examples of heterocycles in fused-ring natural products and examples of historical and/or commercial value are examined …

Preparation Of Enantioenriched Alkyltin Species And Their Application In Stereospecific Transformations, Glenn O. Ralph

Dissertations, Theses, and Capstone Projects

Organometallic reagents containing the tin-carbon bond are used extensively in modern synthetic chemistry for the formation of new bonds to carbon. Over recent decades, transition metal catalyzed cross coupling reactions between two C(sp²) centers have been widely developed. However, the introduction of a C(sp³) center complicates the catalytic cycle, and opens unproductive chemical pathways which lead to isomerization, elimination, and racemization. Our lab has developed a modified-Stille reaction to combat the deleterious effects of β-hydride elimination. Our protocol enables unactivated 2° alkyl organotin nucleophiles to undergo efficient cross coupling reactions with C(sp²) electrophiles, avoiding …

Mild Synthesis Of Perylene Tetracarboxylic Monoanhydrides With Potential Applications In Organic Optoelectronics, Xizhe Zhao

Dissertations, Theses, and Capstone Projects

Perylene tetracarboxylic derivatives are considered good n-type semi-conductors. In past decades, there has been extensive study on their synthesis and electronic properties. Because of the high electron affinity, the ability to form π-π stacks, they have been widely utilized in organic photovoltaic solar cells, field-effect transistors and light-emitting diodes. Many of those applications prefer unsymmetrically substituted perylene tetracarboxylic derivatives. Perylene monoanhydrides are the most versatile intermediates for the preparation of unsymmetrically substituted perylene tetracarboxylic derivatives. In this thesis, I focused on introducing new synthesis methods for perylene monoanhydrides with labile functional group and their potential applications in organic optoelectronics.

In …

An Investigation Of Alkylboron Transmetallation In Palladium-Catalyzed Suzuki Reactions, Benjamin Murray

Dissertations, Theses, and Capstone Projects

Through the past 40 years, carbon-carbon cross-coupling reactions have greatly enhanced the ability of chemists to synthesize C(sp²)-C(sp²) bonds and more recently C(sp²)-C(sp³) bonds. In particular, the Suzuki reaction has proven to be invaluable with its high yields, good functional group tolerance, and low toxicity of reagents. One of the component steps of the catalytic cycle of this reaction is transmetallation, in which the nucleophilic species transfers its organic component to the metal center (generally palladium). The mechanism of transfer from primary alkylboron nucleophiles was studied in the 1990's via use of …

Synthesis And Evaluation Of Novel Iodine-124 Labeled Nucleoside Analogs As Pet Imaging Agents To Predict Response To Gemcitabine Therapy, Kishore Kumar Gangangari

Dissertations, Theses, and Capstone Projects

Gemcitabine (gem) is a nucleoside analog that is used to treat pancreatic cancers (PaCa), which have dismal prognosis and low survival rate. Though gem is used as first line of treatment for PaCa, the response rate is quite low (~30%). Currently, there is no a priori way to determine a responder from a non-responder to gem therapy either invasively or non-invasively. Any biomarker that can act as a prognostic indicator of gem response will greatly aid in selecting responsive patients to gem therapy and provide alternative options such as Folfirinox or other treatments to resistant patient population. Amongst various known …

Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang

Dissertations, Theses, and Capstone Projects

Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …

Copper-Mediated N1-Arylation Of Benzotriazoles, Magdalena R. Andrzejewska

Dissertations and Theses

Benzotriazoles are group of bicyclic heterocyclic compounds that contain three nitrogen atoms fused to a benzene ring. Along with their derivatives, they possess a wide range of properties. They are used in medical field, as they exhibit such properties as antibacterial,antiplasmoidal,antiprotozoal, antifungal and anti-inflammatory activities, among others. They are also used in various industries as herbicides, UV absorbers, deicing and antiicing agents and corrosion inhibitors, to list a few. Because of their wide range of applications, we designed a new two-step synthesis for the formation of N-1-aryl benzotriazoles. 1-Hydroxy-1H-benzotriazole N-oxides were synthesized using phenylboronic acid (PhB(OH) …

A Stereospecific Pd-Catalyzed Suzuki Cross-Coupling Reaction And A Statistical Study Of The Ligand's Role In Stereoselection, Shibin Zhao

Dissertations, Theses, and Capstone Projects

The development of palladium-catalyzed carbon-carbon cross-coupling reactions has profoundly influenced the manner through which we approach the synthesis of complex organic molecules. Among established cross-coupling reactions, which include Kumada, Negishi, and Stille reactions, the Suzuki cross-coupling reaction exhibits particularly wide functional group compatibility, while employing non-toxic, air-stable organoboron nucleophiles. Conventional studies of Pd-catalyzed Suzuki cross-coupling reactions have focused on C(sp²)-C(sp²) cross-coupling reactions, which result in the formation of planar products. Conceptually, the use of C(sp³) (secondary) nucleophiles would enable the reliable manipulation of organic molecules in three dimensions. However, this process has not been …

Synthesis And Evaluation Of Densely-Functionalized Troponoids, Danielle R. Hirsch

Dissertations, Theses, and Capstone Projects

Herein, we document our efforts to expand the scope of troponoid synthetic methodology towards densely-substituted scaffolds. This body of work has focused primarily on an oxidopyrylium cycloaddition/ring-opening strategy for the synthesis and biochemical evaluation of troponoids for assistance in a variety of medicinal chemistry studies. In Chapter 1, we outline the use of this synthetic strategy in the profiling of a library of synthetic αHTs against an aminoglycoside antibiotic resistance enzyme known as aminoglycoside-2’’-O-nucleotidyltransferase [ANT(2’’)-Ia]. Enzymatic mechanistic insights have been gleaned from an assessment of troponoid/antibiotic synergistic potential. In particular, two synthetic constructs were identified as promising antibiotic adjuvant candidates, …

Deciphering The Mechanism Of O2 Reduction With Electronically Tunable Non-Heme Iron Enzyme Model Complexes, Roshaan Surendhran, Alexander A. D'Arpino, Bao Y. Sciscent, Anthony F. Cannella, Alan E. Friedman, Samantha N. Macmillan, Rupal Gupta, David C. Lacy

Publications and Research

A homologous series of electronically tuned 2,20,200-nitrilotris(N-arylacetamide) pre-ligands (H3LR) were prepared (R ¼ NO2, CN, CF3, F, Cl, Br, Et, Me, H, OMe, NMe2) and some of their corresponding Fe and Zn species synthesized. The iron complexes react rapidly with O2, the final products of which are diferric mu-oxo bridged species. The crystal structure of the oxidized product obtained from DMA solutions contain a structural motif found in some diiron proteins. The mechanism of iron mediated O2 reduction was explored to the extent that allowed us to construct an empirically consistent rate law. A Hammett plot was constructed that enabled …

Discovery And Development Of A Three-Component Oxidopyrylium Cycloaddition And Its Application Towards Alpha-Hydroxytropolone Synthesis, Michael P. D'Erasmo

Dissertations, Theses, and Capstone Projects

Historically, natural products have provided unique research opportunities and challenges for organic synthesis, chemical biology, and medicinal chemistry due to their molecular complexity and effects on physiological systems. The total synthesis of natural products has not only produced novel reaction methods and strategies capable of efficiently generating complex structural motifs but also granted access to sufficient quantities of otherwise scarce natural product material for clinical evaluation. These synthetic efforts have facilitated the formation of a transdisciplinary partnership between chemistry, biology, and medicine that has been paramount in elucidating the chemical and pharmaceutical utility of natural products. Chapter I of this …

Organic Photochemistry: Remote Delivery Of Reactive Oxygen Intermediates Via A Heterogeneous Approach, Niluksha Walalawela Abeykoon

Dissertations, Theses, and Capstone Projects

Photosensitized oxidation reactions produce a number of intermediates species, which are generated in varying amounts over time. This complexity presents major challenges in the study of oxidation processes. Mechanistic efforts to separate and deliver reactive oxygen intermediates enable their controlled use in processes such as bacterial inactivation. This thesis describes a heterogeneous reaction approach taken to control the generation and delivery of reactive oxygen intermediates. The mechanistic details of photosensitized reactions were elucidated via synthetic, materials, and physical organic techniques to optimize the delivery of reactive oxygen intermediates. This thesis contains six chapters as described below.

Chapter 1 gives a …

Experiential Learning Activity: Biodiesel Inquiry Project, Ji Kim

Open Educational Resources

The activity described herein can be implemented in introductory chemistry and high school chemistry courses. The main goal of the project is to integrate a ubiquitous biodiesel production with experiential learning by providing a community-based project. The students work in groups, research the benefits of using biodiesel over petroleum-based diesel, collect waste cooking oil from home or restaurants, develop simple and cost-effective methods to produce biodiesel.

Synthesis Of A Model Of The Bc Ring System Of Oxygenated Angucyclines, Xiaolan Wu, Abdullah Allaoa, Tony E. Nicolas

Publications and Research

Angucycline is a subclass of natural antibiotics, containing a characteristic tetracyclic ring structure, and featuring a wide range of biological functions, including antitumor, antiviral and antifungal properties. This extraordinarily therapeutic character has interested many chemists to develop efficient methodologies for synthesizing the tetracyclic ring system of angucycline. Construction of the BC ring configuration appears as a synthetic challenge. Successful installation of hydroxyl groups at the AB junction would pave the way for efficient syntheses. As a continuation of the previous work done on this system, our synthetic methodology focuses on the coupling of a suitably substituted Phthalide and an activated …