Efforts Towards The Asymmetric De Novo Synthesis Of Lanostanes And Euphanes, Htoo Tint Wai

Dartmouth College Ph.D Dissertations

Tetracyclic triterpenoids are ubiquitous in nature and biology, with members displaying a wide range of medically relevant properties and occupying rather distinct regions of chemical space. Members of this large class include well-known steroid hormones and sterols as well as structurally interesting subclasses such as lanostanes and euphanes, among others. Comprised of the tetracyclic skeleton with three stereodefined quaternary centers at ring-junction positions, lanostanes and euphanes present synthetic challenges that are different from those encountered in efforts targeting the structurally less complex steroid hormones. Lanostanes, in particular, stand as a historically important class of compounds as significant attention has been …

Nano-Engineered Soft Magnets: Potential Application In Water Treatment, Hyperthermia And Molecular (Organic) Magnets, Yohannes Weldemariam Getahun

Open Access Theses & Dissertations

Scrutinizing the remarkable and tunable properties of magnetic materials at a nanoscale size "There's Plenty of Room at the Bottom..." Richard Feynman, this study attempts to find sustainable solutions to some of the deteriorating environmental, health, and energy problems the world is encountering. Due to their simple preparation, surface adaptability, and tunable magnetic and optical properties, magnetic nanoparticles have been extensively investigated in water treatment, cancer therapy, data storage, and more. However, relying on non-reusable and chemical-based treatment agents in water, complex and costly cancer treatment procedures and molecular magnets that operate far below room temperature limited those attempts from …

Synthesis Of Novel Dna-Binding Polyamides To Prevent Cancer-Related Gene Overexpression, Huy Q. Nguyen

Dissertations

Pyrrole-imidazole polyamides (PIPs) are nanomolecular compounds designed to fit in the tight space of DNA minor grooves. As analogs of Netropsin and Distamycin A, PIPs are specifically designed to recognize the base pairs of DNA sequences. PIPs have many biological applications, such as regulating gene expression, biochemistry pathway regulations, and suppressing the development of cancer cells. SETMAR gene is the chimeric fusion of the SET domain with the mariner transposase. Its protein (Metnase) has functions involving DNA repairs in the NHEJ pathway, regulating gene expression, DNA decatenation, etc. Despite not having an active transposable element, SETMAR still has an unknown …

Development Of Plasmonic And X-Ray Luminescence Nanoparticles For Bioimaging And Sensing Applications, Meenakshi Ranasinghe

All Dissertations

This dissertation discusses the development of plasmonic and X-ray luminescence nanoparticles (~100 nm) to use in bioimaging and sensing applications. The nanoparticles have interesting optical properties compared to their atomic levels and bulk materials. The optical properties of nanomaterials can be controlled by changing size, shape, crystal structure, etc. Also, they have a large surface area that can be functionalized with biomolecules. Therefore, the optical properties and biofunctionalized nanomaterials are useful in biomedical applications such as targeted drug delivery, bioimaging, and sensing. The overall theme is to use nanoparticles with interesting optical properties compared to their atomic levels and bulk …

Pyridyl Bis-Urea Macrocycles As Supramolecular Synthons And The Design And Synthesis Of Small Molecule Pharmaceuticals Targeting Ly6k, Devan D. Buchanan

Theses and Dissertations

Assembled pyridyl bis-urea macrocycles have been utilized as 1D supramolecular synthons to construct hierarchical assemblies. These macrocycles have both urea and pyridyl functional groups and can form non-covalent interactions with hydrogen or halogen bond donors through symmetric, ditopic acceptor motifs. Bis-urea macrocycles offer interesting capabilities as synthons to organize donors into well-defined crystal structures. In part, this is due to the urea motifs’ propensity to assemble through hydrogen bonding. New, asymmetric pyridyl macrocycles were synthesized, crystallized, and experimentally probed to determine how symmetry affects their assembly and utility as supramolecular synthons.

The Uphadhyay group identified small molecules, including NSC11150, …

Synthesis And Applications Of Α,Β-Dehydroamino Acid-Containing Peptides, Diego A. Moya

Theses and Dissertations

Yaku’amide A (YA) is a linear anticancer peptide that is rich in bulky dehydroamino acids (ΔAAs) and β-hydroxyamino acids (β-OHAAs). In our recent total synthesis of YA, we featured a one-pot anti dehydration–azide reduction–O→N acyl transfer process for the stereospecific construction of Z- and E- ∆Ile residues. Despite previous total syntheses and our efforts, the synthesis of YA remains lengthy. Via computational studies, we identified two analogue peptides that closely resemble the conformation of YA. The use of simpler and symmetrical bulky ΔAAs such as dehydrovaline (ΔVal) and dehydroethylnorvaline (ΔEnv) as surrogates of ∆Ile, along with azlactone chemistry for their …

Trichloroacetimidates As Outstanding Electrophiles For The Carbon-Nitrogen, Carbon-Oxygen And Carbon-Carbon Bonds Formation And Synthetic Studies Of Protein Phosphatase-5 (Pp5) Small Molecule Inhibitors, Nilamber Mate

Dissertations - ALL

Trichloroacetimidates have been previously used for glycosidic bond formation in carbohydrate chemistry and in Friedel-Craft reactions. Traditionally, trichloroacetimidates had be synthesized using an alcohol and strongly basic conditions, but in recent years milder preparation methods have been reported. Given the ease of preparation of these versatile reagents, their chemistry has been explored intensely in recent years. While few reported methods suggest they can react under promoter free conditions, activation by Lewis or Brønsted acid leads to a formation of a carbocation from benzylic trichloroacetimidates. Work described herein makes use of these convenient carbocation precursors for new reactions.Isatin is an ambidentate …

Synthetic Investigations In Chemical Probe Development Part 1: Design And Synthesis Of Novel Triton X-405 Adenosine Conjugates; Part 2: Synthesis Of 2,8-Dihydroxychrysene, Rachel Irene Hammond

Honors Theses

Although not drugs themselves, chemical probes are a necessary tool in biomedical research for the interrogation of biological systems. In the present synthetic investigation, two chemical probes were developed – a Triton X-405 adenosine conjugate (TX-405A) and 2,8-dihydroxychrysene. The designed TX-405A conjugate was generated in four steps through tosylation and amination of TX-405 such that EDC-coupling of TX-amine with 2’,3’-Isopropylidene adenosine-5’-carboxylic acid afforded TX-405A following acetonide deprotection. The development of TX-405A represents the first report of the synthesis and utilization of a detergent-linked dosimeter. The synthesis of 2,8-dihydroxychrysene provided an in-depth exploration on the unique reactivity of chrysene. The desired …

Synthesis And Characterization Of Ternary Pt Nanoally Catalysts For Fuel Cells, Ylith Peck

Undergraduate Honors Theses

A hydrogen fuel cell is an electrochemical device that converts oxygen and hydrogen into electrical energy while producing water as the only by-product, which has attracted growing interest, especially in the automotive industry. This technology is efficient and has zero pollution to the environment, in contrast to the direct use of fossil fuels in combustion engines which produce pollution and greenhouse gas emissions. One of the key components for hydrogen fuel cells is the catalyst that operates at the cathode, which currently use platinum. Due to the scarce amount of platinum in the world, the manufacturing cost for fuel cells …

Part I: Synthesis Of Quinolones For Inhibition Of The Β-Barrel Assembly Machine In Gram Negative Bacteria; Part Ii: Synthesis Of Azo Dye Sensors For Detection Of Metal Ions In Aqueous Environments, Katryna Williams

Theses and Dissertations

Part I: Antibiotic resistance in Gram-negative bacteria is a growing cause of concern worldwide. Thousands of people die from antibiotic resistant bacteria every year. The β-Barrel Assembly Machine (BAM) in Gram-negative bacteria plays a role in antibiotic resistance as its porin, BamA, can regulate which molecules enter the cell, meaning it can prevent antibiotics from entering the bacterial cell. BamA exists in an open and closed form and is only selective in its closed form. BamA opens and closes through the H-bonding of two intramolecular β-strands. It is theorized that the creation of a β-sheet mimetic, based on work done …

Design, Synthesis, And Analysis Of Paired Coiled-Coil Peptidic Molecular Building Blocks Used For Linearly Controlled Self-Assembly Of Α-Helical Coiled-Coil Heterodimer Peptide Pairs, Jason Distefano

Chemistry Theses

Molecular building blocks are fundamental to biological synthesis and processes and have been utilized in advanced materials, drugs and drug delivery systems, and biotechnology. Proteins have been used as molecular building blocks for the construction of complex, well-ordered structures. Coiled-coil protein domains are essential subunits used for the oligomerization of protein complexes, gene expression, and structural elements of biological materials. The synthesis and assembly of proteins utilizing coiled-coil motifs are of great scientific interest due to their potential applications in disease treatment, biomechanical motors, nanoscale delivery systems, etc. However, assembling protein complexes with specific morphology is still challenging because …

Synthesis And Characterization Of Enantioenriched Deuterated And Fluorinated Small Molecules, Mitchell D. Mills

Master's Theses (2009 -)

The development of novel deuterated and fluorinated bioisosteres has significantly impacted the pharmaceutical and agricultural industry and created a growing demand for new synthetic methodology. Both deuterated and fluorinated small molecules exist at the forefront of drug discovery due to their unique ability to attenuate the pharmacokinetic properties of new and currently existing drugs. Selective, high-throughput methods for deuteration and fluorination are scarce in the literature, especially methods that introduce D or F atoms asymmetrically. Benzylic CH bonds are oftentimes key sites for enzymatic manipulation in metabolic processes, alteration of CH bonds to CD or CF bonds at the benzylic …

Antibacterial Activity, Structure-Activity Relationships, And Scale-Up Reaction Of 1,3,4-Oxadiazoles, Olivia Marie Smith

Undergraduate Honors Thesis Projects

Oxadiazoles are compounds in the field of organic chemistry that have been gathering interest in the medicinal chemistry and microbiology communities for their biological properties, which range from anti-inflammatory agents, to chemotherapy drugs, to antibiotics. The synthesis of oxadiazoles can be difficult due to the expensive and complex nature of the techniques used as well as the volatile reagents and elevated temperatures that are often required in organic synthesis. The Grote lab has recently developed a new method for the synthesis of 1,3,4-oxadiazoles under mild conditions. The goals of this thesis were thus twofold: to develop a viable scale-up procedure …

A New Way To Make Music: Processing Digital Audio In Virtual Reality, Gavin E. Payne

Senior Projects Spring 2022

The work of this project attempts to provide new methods of creating music with technology. The product, Fields, is a functional piece of virtual reality software, providing users an immersive and interactive set of tools used to build and design instruments in a modular manner. Each virtual tool is analogous to musical hardware such as guitar pedals, synthesizers, or samplers, and can be thought of as an effect or instrument on its own. Specific configurations of these virtual audio effects can then be played to produce music, and then even saved by the user to load up and play with …