Alumni Dissertations and Theses

 
 

Alumni Dissertations and Theses

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  • Synthesis, Fabrication and Characterization of Magnetic and Dielectric Nanoparticles and Nanocomposite Films

    Author:
    Xiaohua Liu
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Stephen O'Brien
    Abstract:

    Materials science is an interdisciplinary field investigating the structure-property relationship in solid-state materials scientifically and technologically. Nanoscience is concerned with the distinctive properties that matter exhibits when confined to physical dimensions on the order of 10-9 meters. At these length scales, behaviors of particles or elaborate structures are often governed by the rules of quantum mechanics in addition to the physical properties associated with the bulk material. The work reported here seeks to employ nanocystals, binary nanocomposites and thin films of materials, to build versatile, functional systems and devices. With a focus on dielectric, ferroelectric, and magnetoelectric performance, a series of materials has been synthesized and different types of nanocomposites have been built. Barium strontium titannate particles at various sizes was developed, aiming at high dielectric constant and low loss at high frequency range. Cobalt ferrite-polymer nanocomposite was fabricated with potential magnetoelectric coupling. Along with synthesis, advanced electron microscopies (TEM, SEM, STEM, EELS) at atomic resolution were employed to thoroughly investigate the crystallinity, morphology and composition. By means of spin-coating and printing techniques, single and multiple layered capacitors featuring improved dielectric performance (high k, low loss, high breakdown voltage, etc.) were developed through a) electrode deposition, b) dielectric layer deposition, and c) parylene evaporation. Such capacitors are further incorporated into electric power converters for LED lighting. Hopefully in the future we can make electronic devices more efficient, sustainable, smaller and cheaper. By advancing our knowledge of nanomaterials, especially those with potential of multifunction, energy efficiency and sustainability, we have strived to push the limits of synthesis, characterization, fabrication and property analysis of nanostructures towards new, reliable and low-cost multifunctional systems. Some of our efforts are described in the following chapters.

  • Synthesis of C-Glycoside Analogs of the Immunostimulatory Glycosphingolipid, alfa-Galactosylceramide

    Author:
    Zheng Liu
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    Robert Bittman
    Abstract:

    This dissertation presents the asymmetric total synthesis of immunostimulatory &alpha-C-galactosylceramide (&alpha-C-GalCer) glycolipids and D-ribo-phytosphingosine. Also included in this dissertation is an improved two-step synthetic route to primary allylic alcohols from aldehydes and verification of configurations of three contiguous stereogenic centers in the phytosphingosine backbone of &alpha-1C-GalCer, the nonisosteric analog of &alpha-C-GalCer in which the glycosidic oxygen atom linking the sugar with phytosphingosine is deleted.. Chapter 1 presents an improved two-step synthetic route to primary allylic alcohols from aldehydes. A modification of the Horner-Wadsworth-Emmons (HWE) olefination reaction in H2O/2-propanol (1:1) and a convenient protocol to prepare AlH3 in tetrahydrofuran from LiAlH4 and n-butyl bromide are the key factors in the improvement. Chapter 2 presents an asymmetric synthesis of D-ribo-phytosphingosine. The synthesis was achieved by utilizing the ProPhenol-catalyzed alkynylation of an unsaturated aldehyde to afford an allylic propargylic alcohol followed by asymmetric epoxidation and opening of a propargylic epoxy alcohol with NaN3/NH4Cl. Deprotection and reduction of the resulting acyclic azide then gave D-ribo-phytosphingosine. The acyclic azide was also subjected to an intramolecular click reaction, generating a bicyclic triazole, whose diacetate derivative was found to have almost identical cis and trans vicinal coupling constants. The relative stereochemistry of the final product was assigned by NMR analysis of corresponding Mosher esters and amides, and confirmed by comparison of NMR spectra and specific rotations of its tetraacetate derivative with reported data. The stereochemical assignment based on comparing J values with reported data in bicyclic triazoles, generated by a copper-free intramolecular click reaction, was inconclusive. Alkynyl-azide, an efficient glycosyl acceptor in the synthesis of &alpha-galactosylceramide derivatives, was also readily prepared by this route. Chapter 3 presents (1) a modification of the first generation synthesis of &alpha-1C-galactosylceramide featuring the two-step HWE olefination and alane reduction protocol described in Chapter 1 and the ProPhenol-catalyzed asymmetric alkynylation reaction, and (2) a detailed verification of the configurations of three contiguous stereogenic centers in the phytosphingosine moiety. Given the possible intramolecular participation by the 2'-O-benzyl group of the galactosyl moiety in epoxide opening by the azide anion, an attempt was made to assign the relative stereochemistry of the azide-bearing carbon through the coupling constants (J4,5 and J5,6) in a bicyclic triazole, which was obtained via an intramolecular click reaction and acetylation of diol. The cis J4,5 and trans J5,6 displayed almost the same values, suggestive of possible retention in the opening of the epoxide; however, nOe analysis was inconclusive. Model compounds containing the same bicyclic triazole skeleton were prepared via the same reaction sequence, and their cis J4,5 and trans J5,6 coupling constants showed similar values as to those in the sugar counterpart. According to the systematical investigation of the model compounds described in Chapter 2, the epoxide-opening reaction did indeed proceed with inversion. These results exclude intramolecular participation by the 2'-O-benzyl group and emphasize the need for caution when coupling constants alone are used to judge the relative configuration in bicyclic triazoles and related systems. Chapter 4 presents stereocontrolled syntheses of &alpha-C-GalCer and its &alpha-C-acetylenic analog from 1-hexadecene and D-galactose. The key transformations include Sonogashira coupling, Sharpless asymmetric epoxidation, and Et2AlCl-catalyzed cyclization of an epoxytrichloroacetimidate to generate a protected dihydrooxazine synthon.

  • Dynamics and Kinetics of Singlet Oxygen Mediated Oxidation of Methionine in the Gas Phase, Hydrated Clusters and Solution

    Author:
    Fangwei Liu
    Year of Dissertation:
    2015
    Program:
    Chemistry
    Advisor:
    Jianbo Liu
    Abstract:

    The reaction between methionine (Met) and electronically excited singlet molecular oxygen (O2[a1Δg]) has been investigated in a systematic fashion, using a home-built electrospray ionization (ESI) guided-ion-beam tandem mass spectrometer (MS). The study started from probing the reaction dynamics between the isolated protonated/deprotonated methionine ions with 1O2 in the gas phase, transited through the same systems micro-solvated with explicit water molecules in gaseous hydrated clusters, and concluded with real-time methionine oxidation kinetics determination in aqueous solution. The reaction products, cross sections, and collision energy dependence were measured by ESI-MS. Density functional theory (DFT) calculations, Rice-Ramsperger-Kassel-Marcus (RRKM) statistical modeling and direct dynamics simulations were carried out to construct the potential energy surface (PES) along their reaction coordinates (including reactants, intermediate complexes, transition states, and products), analyze thermodynamics and energy barriers, as well as provide insight into the different types of stabilization of reactive species upon oxidation. In project 1, in order to elucidate the charge effects on the reaction mechanism, the reaction were explored between 1O2 and gas-phase dehydrated methionine in both protonated (MetH+) and deprotonated ([Met - H]-) ionization states. For the reaction of MetH+ + 1O2, the product channel corresponds to generation of hydrogen peroxide via transfer of two hydrogen atoms from MetH+ to singlet oxygen. The reaction is mediated by a precursor and/or hydroperoxide intermediate, and is sharply orientation-dependent. The reaction cross section shows strong inhibition by collision energy. No oxidation products were observed in the reaction of [Met - H]- + 1O2, albeit the reaction is mediated by similar hydroperoxides. Due to the high energy barriers in the product exit channels, these nascent hydroperoxides cannot evolve to stable end products at the collision energy range in the present study, but decayed back to reactants. Project 2 explored the reaction between 1O2 and hydrated protonated/deprotonated methionine clusters (MetH+(H2O)1,2/[Met - H]-(H2O)1,2), aiming at probing the effects of charge and hydration states on the reaction mechanism, as well as mimicking the micro-solvation environment in biological systems. For the reaction of MetH+(H2O)1,2 + 1O2, besides producing hydroperoxides (and their hydrates), an H2O2 elimination mechanism was observed. This observation indicates a transition from the gas-phase oxidation pathways to solution-phase reactions. In contrast to the non-reactivity of its dehydrated counterpart, [Met - H]- becomes oxidizable once it is hydrated by water(s); hydroperoxides and their hydrated species were captured as the oxidation products in the reactions of [Met - H]-(H2O)1,2 + 1O2. In the last project, a solution-phase reaction setup, which couples the 1O2 generation and detection system to our ESI-MS, was developed. This on-line apparatus minimizes the sample transfer time between reaction and mass spectrometry measurements. It enables us to identify the oxidation products of Met in different pH solutions, and follow real-time reaction profiles for determining their reaction rates. Met-O is the dominant oxidation product in acidic and neutral solutions, whereas [Met - H]--O and dimeric product [Met - H]--O-Met dominate in basic solution despite with lower reaction rates. The calculated reaction rate constants are 6 × 109 M-2⋅s-1 in acidic solution and 2 × 109 M-2⋅s-1 in basic solution, respectively.

  • Enhanced Raman Effect on MBE Grown Semiconductor Quantum Dots

    Author:
    Richard Livingstone
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    John Lombardi
    Abstract:

    Using Surface Enhanced Raman Spectroscopy (SERS), I observed Raman enhancements (104-105) for pyridine, 4-tertbutylpyridine and other biological molecules adsorbed on a II-VI semiconductor CdSe/ZnBeSe sample of uncapped self-assembled quantum dots produced by molecular beam epitaxy. When a monolayer of Raman active molecule is adsorbed on these structures, excitation at 488 nm produces intense Raman spectra and a very large enhancement of the a1, b1 and b2 modes. This indicates the presence of charge-transfer as a contributor to the enhancement. Furthermore, the excitation wavelength is in the vicinity of several interband transitions located both in the quantum dots and the wetting layer, and it is likely that these resonances also contribute to the enhancement factor. The observed enhancement is among the largest yet seen on semiconductor quantum dot systems and is the first obseved on MBE grown quantum dots. The observed Raman spectrum shows several differences from the normal Raman spectrum, and is closer in some ways to the SERS observed on Ag nanoparticles. Among other things, the prominence of non-totally symmetric lines indicates the importance of charge-transfer contributions to the overall enhancement. In Ag nanoparticle SERS, both the charge-transfer and surface plasmon resonances have been shown to be responsible for the effect. However, in semiconductors, the excitation wavelengths are far from the region of surface plasmon resonance for CdSe and so the magnitude of enhancement must be attributed to other possible resonances. Bandgap dependence studies using 4-tertbutylpyridine on semiconductor quantum dots with varying bandgap energies, indicates that transitions to the bandgap are important contributors to the overall enhancement, and may possibly be regarded as a replacement for the surface plasmon resonance so important in metallic SERS. As in SERS, however, the observation of non-totally symmetric bands indicates additional contributions from charge-transfer resonances. It is most likely a combination of these two effects which is responsible for the rather large enhancements observed here.

  • Energy of the Quasi-free Electron in Repulsive Atomic and Molecular Fluids

    Author:
    Yevgeniy Lushtak
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Cherice Evans
    Abstract:

    The ability to predict accurately the energy V0<\sub>(ρ) of the quasi-free electron along the entire density V0<\sub>(ρ) range of a supercritical fluid has applications in determining the ideal thermodynamic conditions for chemical reactions involving charged species. The previously established field ionization method of extracting V0<\sub>(ρ) from the fluid density dependent shift Δ(ρ) in the ionization energy of a dopant molecule has led to the discovery of a novel effect on V0<\sub>(ρ) occurring near the critical isotherm of the fluid. Unfortunately this method has limitations in determining V0<\sub>(ρ) in fluids with low critical temperatures as well as fluids opaque to vacuum ultraviolet radiation. Thus, accurate determination of V0<\sub>(ρ) in repulsive fluids (i.e., those possessing a positive zero kinetic energy electron scattering length) using field ionization is difficult. The new method developed in this study, namely field enhanced photoemission, allows for the direct determination of the quasi-free electron energy from the density dependent shift in the work function of a metal electrode submerged in the fluid. This mitigates the problems posed by field ionization while producing results with iii similar precision. Field enhanced photoemission was verified by measuring V0<\sub>(ρ) of Ar, an attractive fluid (i.e., one with a negative zero kinetic energy electron scattering length) studied extensively in the past by field ionization, before applying the method to the study of V0<\sub>(ρ) in the repulsive fluids Ne, He and N2. The new results showed a distinct critical point effect on V0<\sub>(ρ), which was accurately modeled with the local Wigner-Seitz approach developed for attractive fluids. Thus, this work extends our theoretical model to repulsive fluids. Unlike the attractive fluids studied in the past, the quasi-free electron energy in the repulsive fluids presented here is strictly positive. A careful analysis of the terms contributing to V0<\sub>(ρ) within the local Wigner-Seitz model leads one to expect the quasi-free electron energy to be positive in repulsive fluids in general. A discussion of fluid density dependent behavior of the kinetic and potential energy terms contribut- ing to V0<\sub>(ρ) is presented along with an explanation of the evolution of the shape of the V0<\sub>(ρ) curves for the fluids studied.

  • DESIGN, SYNTHESIS, AND ANTI-TUMOR ACTIVITIES OF BENZOPOLYSULFANE COMPOUNDS THAT MIMICS A TUNICATE-DERIVED NATURAL PRODUCT

    Author:
    Adaikapillai Mahendran
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    ALEXANDER GREER
    Abstract:

    Benzopolysulfanes are untapped potential therapeutic compounds, which possess an impressive array of biological activities. By developing an entirely new class of compounds (polysulfanes) drug resistance can be evaded due to the lack of exposure of organisms to these compounds. However, polysulfanes are challenging compounds to prepare, and usually have very poor water-solubility. New synthetic methods and studies on solubility and cell-directed delivery are needed to explore the range of possibilities of this novel class of compounds. This thesis outlines (1) synthesis and biological activities of benzopolysulfane conjugates namely, PEGylated benzopoylsulfanes; and (2) mechanistic aspects on mode of introduction of sulfur atom to the catechol core; Benzopolysulfanes, 4-CH3(OCH2CH2)3NHC(O)-C6H4-1,2-Sx (x = 3-7, and 9) were synthesized with a PEG group attached through an amide bond and examined for water solubility, antitumor activity, and propensity to equilibrate and desulfurate. LCMS and HPLC data show the PEG pentasulfane ring structure predominates, and the tri-, tetra-, hexa-, hepta-, and nonasulfanes were present at very low concentrations. The presence of the PEG group improved water solubility by 50-fold compared to the unsubstituted benzopolysulfanes, C6H4Sx (x = 3, 5, and 7), based on intrinsic solubility measurements. Polysulfur linkages in the PEG compounds decomposed in the presence of ethanethiol and hydroxide ion. The PEG pentathiepin desulfurated rapidly and an S3 transfer reaction was observed in the presence of norbornene, no S2 transfer reaction was observed with 2,3-dimethylbutadiene. The antitumor activities of the PEG-substituted benzopolysulfane mixtures were analyzed against four human tumor cell lines PC3 (prostate), DU145 (prostate), MDA-MB-231 (breast), and Jurkat (T-cell leukemia). The PEG conjugated polysulfanes had IC50 values 1.2-5.8 times lower than the parent "unsubstituted" benzopolysulfanes. Complete cell killing was observed for the PEG polysulfanes with 4 µM for PC3 and DU145 cells, and with 12 µM for MDA-MB-231 cells. The results suggest that solubilization of the polysulfur linkage is a key parameter to the success of these compounds as drug leads. A mechanism is proposed for the formation of cyclic 5,6,7,8,9-pentathiabenzoc ycloheptene-1,2-diol, 4, from the reaction of o-benzoquinone with reduced elemental sulfur, H2Sx. 1,6-Conjugate addition to the quinone is favored over 1,4-conjugate addition. Hydrogen bonding to the quinone oxygen enhances the nucleophilicity of H2Sx by facilitating the removal of the S-H proton. We propose that initially formed 3-polysulfidobenzene-diol intermediates, 5, are oxidized to their corresponding quinones, 13, and closure of the polysulfur ring subsequently takes place at the C3-C4 bond leading to 4. A possible mechanism for the formation of pentasulfur linkage in 4 is discussed, which the key moiety is found in a number of natural products.

  • Design of Well-Defined Mesoporous Silicas via Surfactant Templating Method Enhanced by the Use of Swelling Agents

    Author:
    Tiffany Man
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Michal Kruk
    Abstract:

    Surfactant-templated ordered mesoporous materials continue to attract tremendous attention as these materials are characterized by reproducibility and predictability of their synthesis as well as their wide range of potential applications, which serve as future opportunities for additional advancement. The main purpose of this dissertation is to advance the understanding how to control the structural features and properties in the synthesis of well-defined porous materials via surfactant templating method, while keeping in mind that the uniformity of pore size and structural ordering are essential characteristics for these well-defined materials. The work was primarily focused on the issue of the unit-cell size and pore size adjustment in the large-pore domain (that is, for pore diameters above 12 nm) for two-dimensional hexagonal silica structures with cylindrical pores (referred to as SBA-15 silicas). The use of common poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), PEO-PPO-PEO, surfactants, commercially known as Pluronics® in combination with appropriate hydrophobic micelle swelling agents was pursued. The main hypothesis was that it is possible to judiciously select surfactant/swelling agent pairs to achieve optimal structural adjustment capabilities. Moreover, it was hypothesized that different surfactant/swelling agent pairs may work most effectively in certain temperature intervals. The choice of Pluronic tri-block copolymer as main templating agent, the selection of micelle expanders, the adjustment of initial synthesis temperature (including room temperature conditions), and the adjustment of the amount of silica precursor (tetraethylorthosilicate) can systematically affect the structure of porous silica materials formed via the surfactant-micelle-templating synthesis approach. The advancement in pore size tailoring discussed in this dissertation focuses on the above aspects. In particular, considerations based on the extent of solubilization of organic compounds in Pluronic surfactants paved the way to the identification of new excellent swelling agent for the synthesis of large-pore SBA-15. Ordered SBA-15 silica with d100 interplanar spacing of up to about 30 nm has been successfully synthesized. Modifications in the synthesis approach in terms of shortening the duration of the synthesis to as little as six hours and eliminating the need for temperature control to carry out the SBA-15 synthesis were found effective for the synthesis around room temperature. Highly ordered face-center-cubic silica materials have also been synthesized using surfactants with moderate content of the hydrophilic PPO domains challenging our current understanding of viable selections of surfactants for the synthesis of materials with spherical mesopores. These materials exhibited increased mesopore volumes when compared to the silicas obtained via the traditional synthesis of materials with spherical pores involving block copolymers with a high fraction of the hydrophilic PEO domains. Overall, the dissertation demonstrates that the synthesis mixture composition and synthesis conditions can be predictively selected to achieve particular structural properties (such as unit-cell size) or to observe formation of material under particular conditions. Moreover, some additional opportunities emerge as we explore the predictability of the synthesis pathways.

  • Ultra-Large-Pore Ordered Mesoporous Organosilicas and Related Hollow Nanoparticles

    Author:
    Manik Mandal
    Year of Dissertation:
    2010
    Program:
    Chemistry
    Advisor:
    Michal Kruk
    Abstract:

    My dissertation describes the synthesis of ultra-large-pore ordered mesoporous organosilicas and related hollow nanoparticles. In the first part, we developed a versatile approach through which a series of periodic mesoporous organosilicas (PMOs) with 2-dimensional hexagonal structure and different bridging groups can be synthesized. The bridging groups are methylene (-CH2-), ethylene (-CH2CH2-), ethenylene (-CH=CH-), and phenylene (-C6H4-). For this purpose, a combination of a commercially available triblock copolymer Pluronic P123 (EO20PO70EO20) with judiciously chosen micelle swelling agent (cyclohexane, or 1,3,5-triisopropylbenzene) was used as a miceller template, and the initial step of the synthesis was performed at temperature between 10 and 18 oC, followed by hydrothermal treatment at 100-150 oC. The PMOs were characterized using small-angle X-ray scattering (SAXS), nitrogen adsorption, transmission electron microscopy, and solid-state 29Si NMR. For all PMO compositions, the formation of 2-D hexagonal structures with (100) interplanar spacing, d100, up to 21-26 nm was achieved, which is at least seven nanometers larger than d100 reported earlier for any PMO with 2-D hexagonal structure. The nominal (BJH) pore diameters up to 20-27 nm were achieved for the considered compositions of PMOs with with 2-D hexagonal ordering, while even larger pore sizes were sometimes attained for disordered or weakly ordered structures. The mesopores exhibited constrictions or narrow entrances that were widened by increasing the hydrothermal treatment temperature. The pore diameter tended to increase as an initial synthesis temperature decreased, allowing for the pore size adjustment, but the useful temperature range depended on the bridging groups. The present work suggests that the low-temperature micelle-templated synthesis with judicious selected swelling agents is a general pathway to ultra-large-pore 2-D hexagonal PMOs with both aliphatic and aromatic bridging groups. In the second part, we have demonstrated the synthesis of large-pore ethylene-bridged periodic mesoporous organosilica with face-centered-cubic structure. This was achieved by the use of judiciously chosen swelling agents and Pluronic F127 block copolymers at sub-ambient temperature (~ 15 oC). While our work confirmed that 1,3,5-trimethylbenzene (TMB) which was already employed by other researchers, is a facile swelling agent for Pluronic F127-templated ethylene-bridged PMOs with cubic Fm3m structure and our optimization of the synthesis afforded hitherto unreported unit-cell size and pore size for this PMO, it was also demonstrated that swelling agent predicted to have a higher extent of solubilization in Pluronics than TMB provide vast new opportunities. In particular, xylene was found to afford highly ordered materials with large unit-cell size and pore diameter, and a wide range of moderately or weakly ordered materials with very large unit-cell parameters (up to ~ 50 nm) and some with very large pore diameters (up to ~ 20 nm). In this case, the pore size and unit-cell size was tunable by adjusting the amount of inorganic salt (KCl) in the synthesis mixture. The use toluene allowed for the increase in the primary mesopore volume and also afforded large-pore PMOs in the absence of an inorganic salt. The use of the latter was also not required when benzene was used as a swelling agent. The identification of new swelling agents for ethylene-bridged PMO with spherical mesopores is likely to be extendable on PMOs of other framework compositions and for other related materials. In the third part, based on understanding of the condition for the formation of ordered mesoporous organosilicas, we were able to synthesize hollow nanoparticles with different organic bridging groups. Different organic bridging groups such as methylene, ethylene, ethenylene, and phenylene were incorporated in the organosilica walls of the hollow nanoparticles. Further, we were able to synthesize hollow nanotubules comprising of these bridging groups in the walls.

  • Aqueous Solvation of Protein Secondary Structures: Density Functional Theory Study

    Author:
    Mateusz Marianski
    Year of Dissertation:
    2013
    Program:
    Chemistry
    Advisor:
    Joseph Dannenberg
    Abstract:

    In recent years, van der Waals forces have received considerable attention among the scientific community. It is hard to overestimate the significance of dispersion forces which are thought to play important roles in the energetics of biological molecules, such as DNA and peptides. However, the weakest of interactions is also the most difficult to approach by theoretical methods and has been troubling computational chemists for at least last two decades. In my thesis I will answer how well recently developed density functionals deal with the dispersion in the case study of dispersion-enhanced induction complexes, relative stability of pi-stacking and hydrogen bonded dimers, and protein secondary structures. The presented results undermine the belief that recent widely-parametrized and/or dispersion-corrected functionals outperforms older well-established functionals, like famous B3LYP. In the second part of my thesis I will focus on the influence of aqueous solvent on protein structures. Water is present in all biological systems, where it is not only a static medium of the reaction, but also an active part of the process called life, and it requires careful treatment. I compare models of implicit and explicit solvation for beta-turns, alpha-helices, and beta-sheets. I find that solvation by small water clusters can alter the molecular properties of gas phase molecules and continuous methods are not able to model all effects.

  • Oxocarbenium Ion and Alkene Metathesis Strategies for the Synthesis of Complex Cyclohexanes

    Author:
    CLAYTON MATTIS
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    David Mootoo
    Abstract:

    ABSTRACT Oxocarbenium Ion and Alkene Metathesis Strategies for the Synthesis of Complex Cyclohexanes. by Clayton Mattis Mentor: Professor David R. Mootoo Highly oxygenated cyclohexanes comprise the structures of a number of pharmacologically interesting molecules, including potently bioactive natural products and carbapyranosides. The latter, which are unnatural analogues of carbohydrates in which the ring oxygen of the parent sugar is replaced with a methylene group, have attracted interest as hydrolytically stable mimetics of their parent O-glycosides. This research reports the development of two general methodologies for the synthesis of highly oxygenated cyclohexanes: (1) Oxocarbenium Ion Cyclization (OCC) and (2) Ring Closing Metathasis (RCM). Chapter one gives a review of the literature on the synthesis for highly oxygenated cyclohexanes. Previous results from this laboratory have shown that OCCs on cyclic oxocarbeniums derived from 1-thio-1,2-O-isopropylidene precursotrs are highly stereoselective for cyclohexanes and tetrahydropyrans with cis 3,4-diols. To expand the scope of the OCC methodology, the goal was to evaluate the OCCs on non-cyclic oxocarbenium ions derived from mixed thioacetal precursors. Chapter two describes reactions with alkene nucleophiles. In particular, the OCC on an alkene-mixed thioacetal precursor aimed at the cyclohexane core of the immunosuppressive agent FR65814, was examined. This study revealed that OCCs on non-cyclic oxocarbenium ions could deliver cyclohexanes with trans 3,4-diols in high stereoselectivety. As for the previous observations on OCCs with cyclic oxocarbenium ions, these results can be explained in terms of conformational arguments. Chapter three discusses OCCs for non-cyclic oxocarbenium ions and enol-ether nucleophiles. These reactions were expected to give highly oxygenated cyclic enol ether precursors for carba- and C- pyranosides with trans 3,4-diols. However, in all cases, complex mixtures of products that suggested multiple deleterious pathways from the initial formed cyclization intermediates, was observed. This result contrasts to the successful OCCs involving cyclic oxocarbenium ions and enol ethers, and suggests that conformational rigidity is an important requirement for OCCs involving enol ether nucleophiles. Therefore, the OCC strategy appears to be limited to the synthesis of carba- and C- pyranosides with cis-3,4-vicinal diols. Chapter four describes a more general synthesis of carbapyranosides, which is based on the RCM of an enol ether - alkene substrate. This reaction delivers a six-membered cyclic enol ether in which the enol ether oxygen is exocyclic, and contrasts with a related cyclization from the Postema group that provides C-1-substituted glycals, i.e. cyclic enol ethers with an endocyclic enol ether oxygen. This RCM strategy for carbapyranosides was applied to the carba-arabinose and carba-xylose analogues of the sugar residues in the potent antitumor steroidal glycoside OSW-1.