M.Sc. Chemistry

Permanent URI for this collectionhttps://hdl.handle.net/10464/2245

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Exploring the Coordination Chemistry of Hydroxy Alkyl Pyridine and Pyrazine Ligands in 3d Cluster Chemistry
Majidinezhad, Sahar; Department of Chemistry
Three potentially chiral alkoxide ligands, α-methyl-2-pyridine-methanol (mpmH), dimethyl-2-pyridine-methanol (dmpmH) and methyl-2-pyrazine-methanol (mpzmH), are presented together with select 3d ions for the synthesis and study of three novel polynuclear clusters. The first, a {Ni7} complex prepared from chiral-mpmH, has a unique capped trigonal prismatic topology. Magnetostructural studies reveal that at low temperature it has an S = 0 spin ground state and is not an SMM. The second two complexes are both prepared from rac-dmpmH under the same reaction conditions. Dark green, single crystals, of the kinetic product, a {Ni6} cluster were isolated after 2 weeks. This cluster has a structural topology, comprising four edge-sharing cubanes with missing vertices. Magnetostructual studies reveal the cluster is spin frustrated with an S = 2 ground state at low temperature. AC magnetic susceptibility studies are consistent with field induced SMM properties. After two months, blue plates of a {Ni8} cluster, the thermodynamic product, were obtained. The magnetic core of this cluster has a trapezoidal prismatic topology, containing bridging methyl tetrazolate (mtz−) ligands formed via the in situ, NiII-assisted click reaction between the N3− ions and the MeCN solvent. Reaction of mpzmH with Mn benzoate in the presence of azide ions afforded single crystals of a large mixed valence nanosized {Mn22} cluster which has a pyramidal like structural topology comprised of three layers of Mn4O4 and Mn3O4. DC studies are consistent with the presence of 10 MnII and 12 MnIII ions and the presence of dominant antiferromagnetic interactions at low temperature. AC studies reveal an increase in the in-phase susceptibility (χ′) upon cooling, reaching a broad maximum around 4 K, and the emergence of an out-of-phase component (χ″) below 7 K. However, the sample shows very little frequency dependence to the position of the maximum in χ″. Below 2 K there is the beginnings of an uptick in χ″ suggesting the presence of two distinct relaxation processes. The ac data is complex, and not consistent with the slow relaxation behavior typically observed in polynuclear 3d-SMMs.
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Synthesis and structural studies of nucleic acids
Li, Quanjian; Department of Chemistry
The first project focused on the synthesis of 4-15N-2′-deoxycytidine as a tool to study the B- to Z-DNA transition using 15N NMR. This study investigated alternative methods for synthesizing 15N enriched 2′-deoxycytidine at the 4-NH2 position. As a model study, ammonium chloride was used as the 15N source to synthesize 5-methyl-2′-deoxycytidine from thymidine. This chemistry was successfully applied to the synthesis 4-15N-2′-deoxycytidine from 2′-deoxyuridine. In addition, the 15N NMR detection limit was also established to determine the feasibility of studying DNA structures using 15N 1D NMR. The second project involved finding ‘difficult sequences’ in solid-phase oligonucleotide synthesis through phosphoramidite chemistry. Using 18-mers as models, all mathematically possible repeating trinucleotides, dinucleotide, and mononucleotide sequences were synthesized, and the overall yields were analyzed by anion exchange high performance liquid chromatography. It was concluded that depurination was a major contributor to decreased yields in purine-rich sequences. In addition, certain dinucleotide-repeat sequences, especially d(CG) and d(GC), were associated with low overall yields for reasons unknown at this time. The last project involved the identification of alternative detritylation composition for industrial solid-phase oligonucleotide synthesis. These compositions include acids, solvents, and carbocation scavengers. The acid currently used in industrial oligonucleotide solid-phase synthesis is dichloroacetic acid, which has a short shelf life and contains impurities that react with the desired reaction product. For solvents used in the detritylation reaction, toluene and dichloromethane are currently used. While dichloromethane is not preferred in industry, toluene has been known to swell the polystyrene solid support creating an issue during detritylation. Furthermore, the use of carbocation scavengers helps to remove the cleaved DMTr+, preventing it from re-protecting 5′-OH. However, some scavengers have been reported as problematic for this purpose. The results of this project provided a potential alternative acid, namely difluoroacetic acid, investigated and explained the reason for the current solvent choice, and studied the feasibility of scavengers used in the literature.
Open Access
Synthesis and Properties of π- Extended Phenoxyl Radicals.
Wijesundara, Maneesha; Department of Chemistry
Phenoxyl radicals are a class of π-radicals synthesized by single-electron oxidation of phenols. The spin density from the unpaired electron of a phenoxyl radical is highest at the oxyl position, as well as at the ortho and para positions relative to the oxyl group. The stability of phenoxyl radicals can be improved by substituents at the ortho and para positions, including aromatic, O, N, S-alkyl, and sterically hindered alkyl groups, which compensate for electronic deficiency through resonance or inductive effects. In 2016, Lemaire group reported a crystal structure of the stable phenoxyl radical 2,6-bis(8-quinolylamino)-4-(tert-butyl)phenoxyl (BAQP), which lacks the commonly utilized tert-butyl groups at the ortho position relative to the oxyl group. Moreover, the BAQP radical also showed reversible π-dimerization in solution. This thesis describes the synthesis and characterization of two sets of phenoxyl radicals that lack ortho tert-butyl groups, similar to BAQP. The first set of phenoxyl radicals is ortho-substituted with amino derivatives of large aromatic π-systems, namely pyrene, naphthalene, and phenalenone. The second set is the halogenated derivatives of the BAQP radical. This thesis also explores the stability and the reversible π-dimerization of both of the above-described novel sets of phenoxyl radicals. Notably, one of the radicals synthesized during this work, 5-(tert-butyl)l-2-oxy-1,3,-bis(1- prenylamino)benzene, was proven to be stable as crystal structures were obtained from the pure compound. This particular radical, like BAQP, showed reversible π-dimerization in solution detected by spectroscopic methods such as EPR and 1H-NMR spectroscopy methods. The solid- state properties of this radical were also explored through DC susceptibility measurements and EPR spectroscopy.
Open Access
Solvent-free zinc-catalysed hydroboration of esters
Zakarina, Raikhan; Department of Chemistry
This study presents the synthesis of a novel hemilabile bidentate amido phosphine sulfide III-10 ligand and introduces a new synthetic route to the previously reported amido/phosphine III- 12 and amido phosphine oxide III-11 analogues. The present study outlines the synthesis, isolation and characterization of zincII methyl complexes III-13 and III-14 supported by III-10 and III-12, respectively. The catalytic applications of these complexes in the hydroboration of several organic substrates, including esters, nitriles, and quinoline, have been documented. When esters were subjected to the reaction conditions involving III-14 and HBcat, it was shown that ZnMe2 is formed in situ. It was then established that ZnMe2 was an active catalyst for efficient reduction of esters, resulting in moderate to good yields.
Open Access
Investigating the Crosslinking Mechanism of Cinnamate-Modified Silicones
Orshinsky, Alexander; Department of Chemistry
Given the negative impacts of synthetic polymer plastics on the environment, it is of interest to develop syntheses for polymers and polymeric materials that either utilize naturally occurring resources or are biodegradable in an effort to promote sustainability. Cinnamate silicone polymers can be synthesized chemoenzymatically using cinnamic acid, a naturally occurring compound from the oil of cinnamon. Cinnamate side groups are well known photoreactive molecules that undergo [2+2] cycloaddition reactions but whose thermal reactivity was presumed to be forbidden by the Woodward-Hoffmann rules. We have synthesized cinnamate silicones that cure at 110 °C in less than 24 hours to form solid materials via a short-lived free radical reaction that was confirmed using electron paramagnetic resonance (EPR) spectroscopy. The cinnamate silicones were used to produce a series of materials. The properties of the silicone materials and a proposed mechanism for their formation will be discussed.
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DEVELOPMENT OF A SYNTHETIC PROTOCOL FOR THE PREPARATION OF MONO-SUBSTITUTED N-3 FUNCTIONALIZED SYDNONES
Azeez, Oyindamola; Department of Chemistry
This work explores new catalytic methodologies for the synthesis of N-3 monosubstituted sydnone compounds. Sydnones are widely studied for their chemical behaviour, biological and physical properties, and are the most popular mesoionic compounds. Despite the popularity of sydnones, there are still many unexplored approaches for their synthesis and application. Herein is described a simple, novel, one-pot catalytic procedure for the preparation of sydnones. This method utilizes inexpensive commercially available reagents and mild reaction conditions.
Open Access
Stereoselective Synthesis of 1,1',2,2'-Tetrasubstituted Ferrocenes by Double Lithiation of a 1,1'-Disubstituted Ferrocenyl Pyrroloimidazolone
Talisic, Lyzcel; Department of Chemistry
This thesis explores the synthesis of 1,1'-ferrocenyl pyrroloimidazolone for the double diastereoselective lithiation-electrophile quench to yield 1,1',2,2'-tetrasubstituted ferrocenyl compounds. The synthesis followed known literature procedures affording 1,1'-ferrocenyl bisacylazide that then underwent Curtius rearrangement followed by condensation with excess L-proline to yield the desired bishydantoin product. One-pot hydrozirconation/hydrosilylation reaction of the bishydantoin was performed affording the desired chiral pyrroloimidazolone auxiliary. Optimization of the lithiationsubstitution procedure with different amounts of t-BuLi followed by quenching with chlorotrimethylsilane (TMSCl) determined that 4 equivalents of base was necessary to yield predominantly 1,1',2,2'-tetrasubstituted ferrocenyl compounds. Other electrophiles were used to expand the scope of the reaction. The stereochemistry of the tetrasubstituted products was elucidated from X-ray crystallography of the stannane adduct, as well as transmetalation, elimination, and deuteration experiments. It was revealed that the tetrasubstituted products have R-planar (Rp) chirality and the reaction proceeded with high diastereoselectivity (>95:5 dr).
Open Access
THE SYNTHESIS OF SILICON-MODIFIED LIPIDS AND THE INVESTIGATION OF THEIR SURFACE PROPERTIES
Raczywolski, Zachary; Department of Chemistry
This work outlines the synthesis of three novel silatrane-functionalized lipids and the exploration of their capacity to undergo spontaneous particle formation in aqueous environments. The chemoenzymatic synthesis of the lipids required 1,3-diacylglycerides of octanoyl, lauroyl, and palmitoyl acyl chains to be coupled with 1-(3-aminopropyl)silatrane using 1,1’- carbonyldiimidazole and succinic anhydride. These short, medium, and long-chain models were then subjected to dynamic light scattering analysis after vortexing for 15 minutes in concentrations of 15 mg/mL and 30 mg/mL ultrapure H2O. Previous research has demonstrated that hybrid siloxane phosphocholines that possess a disiloxane moiety appended onto a single tail of many biologically relevant double tail phosphocholines are capable of spontaneously forming vesicles of 100 nm in diameter without the need of extrusion or other forceful techniques at these concentrations. For a direct comparison, the chemoenzymatic synthesis of two medium chain hybrid siloxane phosphocholines and a dynamic light scattering analysis of all six previously studied hybrid siloxane phosphocholines were conducted. At concentrations of 30 mg/mL in ultrapure H2O the six-hybrid siloxane phosphocholines spontaneously formed particles ranging from 97.1 nm to 364.3 nm in diameter, but only the medium chain silatrane derivative formed particles of 200 nm in diameter while the short and long chain silatranyl-lipids required extrusion for particle formation. Attempts were made to further expand the library and synthesize silatranefunctionalized phospholipids using a phosphate to couple the tails to the silatrane rather than succinic anhydride. Despite the various trials, the intermediates were observed to rapidly decompose via 31P NMR, 1H NMR, and TLC, likely due to their hydrolytic instability
Open Access
Synthesis of a Photocleavable Bolalipid for the study of the roles of Phospholipid Transfer Proteins and Phosphatidylinositol Lipid Kinases
Wilson, Sean Daniel; Department of Chemistry
This thesis was dedicated to the synthesis of mono- and di-photocleavable phosphatidylcholine bolalipids that were designed to investigate the mechanism of action of the phospholipid transfer protein, Sec14, as well as the phosphatidylinositol 4-kinase, Pik1. While it was the goal of this thesis to synthesize both bola-PCs, only the mono-photocleavable bola-PC was successfully synthesized. The mono-photocleavable bola-PC lipid was designed to contain two glycerol molecules that each had a choline head group connected through a phosphodiester bond at the sn3 position. Each glycerol was acylated with palmitic acid at the sn1 position. These two glycerol moieties were then connected to one another through their respective sn2 hydroxyls via a mono-photocleavable dicarboxylic acid. The initial steps of this work were to synthesize mono- and di-photocleavable diacids to serve as a linker for the polar head groups of the bolalipids. The mono- and di-photocleavable diacids were designed to contain one and two nitrophenyl ethyl photolabile protecting groups, respectively. The synthesis of the di-photocleavable diacid was attempted first, however, these efforts were unsuccessful. Two separate synthetic routes were followed to synthesize this diacid, but neither were viable. Despite this, the synthesis of the mono-photocleavable diacid was successful and was incorporated into a bola-PC. The mono-photocleavable diacid and bola-PC were found to undergo photocleavage when irradiated with 365 nm light, in 60 seconds and 105 seconds, respectively. Photocleavage of the bola-PC was also carried out within a lipid vesicle comprised of 10% bola-PC and 90% DOPC. Spectral and experimental data have been provided for all compounds synthesized. Future efforts will involve the bola-PC synthesized in this thesis undergoing enzymatic conversion into a bola-PI, via the enzyme phospholipase D.
Open Access
Zinc – catalyzed reduction of N – heterocycles
Shakhman, Dinmukhamed; Department of Chemistry
Novel bidentate amine – imine, and amido – imine ligands were synthesized. The former species was reacted with ZnMe2 to generate zinc methyl complex. The compound was fully characterized by 1H NMR and X – ray spectroscopy. The zinc methyl complex demonstrated rather limited catalytic activity in hydroboration and hydrosilylation of N – heterocycles. Consequently, a new zinc hydride complex was synthesized using an amido – imine ligand as a precursor. A series of nitrogen heteroaromatics were successfully hydroborated using catalytic amounts of zinc hydride species. Deuterium – labeling experiments, and kinetic studies allowed to get insights into the reaction mechanism. It was proposed that the hydride transfer proceeds via a six – membered transition state orchestrated by the Lewis acidic zinc – hydride complex. Another project was focused on the synthesis of a potentially redox “non – innocent” diimine ligand, using Arduengo’s diketone as the starting point. Attempts to install an imine moiety resulted in a surprising reaction outcome.
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Approaches Towards a Total Synthesis of Daphenylline
Miskey, Scott; Department of Chemistry
The following work describes the synthesis of advanced intermediates enroute to daphenylline. Construction of the ABCE tetracyclic skeleton of daphenylline was accomplished in thirteen steps with seven percent overall yield from commercially available (S)-carvone through [3,3]-allyl cyanate-to-isocyanate rearrangement, intramolecular Heck Reaction, and Intermolecular Diels-Alder/benzannulation strategies. Efforts towards the synthesis of daphenylline’s D ring are discussed. A terse introduction to the scientific literature of daphniphyllum alkaloids and a comprehensive overview of selected approaches and all previous syntheses of daphenylline is given. Experimental procedures and spectroscopic data are provided for all new compounds.
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Semi-synthesis of Unnatural Narciclasine Derivatives
Thomson, Jared; Department of Chemistry
The generation of new structural derivatives of narciclasine, an Amaryllidaceae alkaloid, has been explored. The strategy applied to the semi-synthesis of these derivatives involves a key enolization step that produces an enol at the C1 position. This material was converted into a triflate to functionalize the C1 position through cross-coupling. Initial triflation attempts resulted in functionalization at C6 instead, and the C6 triflate was successfully coupled with different functionalities. All the novel C6 derivatives were fully deprotected and subjected to evaluation of their biological activity. Experimental and spectral data are provided for all new compounds
Open Access
Synthetic Approaches to C-1 Derivatives of Pancratistatin
Uppalapati, Bhavana; Department of Chemistry
The contents of this thesis describe a synthetic approach towards C-1 derivatives of pancratistatin, utilizing a previously published pathway to access a late-stage cis-diol. The key steps of the approach include enzymatic dihydroxylation to provide the C-ring backbone, Myers’ transposition to convert an allylic alcohol into an olefin, and nucleophilic substitution of a tosylate to insert carbon-based nucleophiles at C-1. Experimental and spectral data are provided for the novel compounds.
Open Access
Hydroamidation of Vinyl Ethers by Acid-Catalyzed Multicomponent Isocyanide Addition
Carlson, Brenden Matthew; Department of Chemistry
Hydroamidation of carbon–carbon double bonds is an attractive strategy for installing nitrogen functionality into molecular scaffolds and, with it, increasing molecular complexity. To date, metal-based approaches have dominated this area of chemical synthesis despite the drawbacks of air and moisture sensitivity, limited functional group tolerance, toxicity, and/or high cost often associated with using metals. Herein is enclosed an operationally simple, metal-free, one-pot, regioselective, multicomponent synthetic procedure for the hydroamidation of carbon–carbon double bonds. This method features mild reaction conditions and utilizes isocyanides and vinyl ethers for the rapid and modular synthesis of α-oxygenated amide scaffolds. Additional effort was put towards synthesizing reactive natural products as substrates to the developed methodology, and drafting a probable catalytic cycle for the main and side reactions present within this multicomponent procedure.
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Synthesis and Evaluation of Trans-bilayer Cross Linking Phospholipids Based on Click (Azide-Alkyne) Chemistry
Hosseini, Yasaman; Department of Chemistry
This thesis describes the synthesis of two phosphatidylcholine (PC) derivatives that are capable of coupling with each other from the alkyl chain through click reaction to form bola-PC. Successful coupling of monomeric phosphatidylcholine derivatives would lead to synthesis of corresponding phosphatidylinositol molecules as future work. PC derivatives that were synthesized in this work were phosphatidylcholine containing terminal azide and terminal alkyne on the alkyl chain of sn2 position. Sn-glycero-3-phosphocholine (GPC) was used as glycerol back bone with two available hydroxyl groups for esterification. The first esterification was done using dibutyltin oxide as catalyst and palmitoyl chloride as acylating agent on the primary hydroxyl group, sn1 position. Secondary hydroxyl group in the sn2 position of GPC was esterified by terminal alkyne and terminal azide fatty acids through Steglich esterification. PC analogues with suitable functional groups for click chemistry were, then, incorporated in the 100 nm-vesicles in buffer solution and exposed to copper catalyst/L-histidine complex and sodium ascorbate solution at room temperature. Formation of bola-PC were observed in the hydrophobic core of lipid bilayer and this was the main objective of this study.
Open Access
N–Phenyl Pyrroloimidazolone Derivatives for Stereoselective Birch Reduction-Alkylation and Chiral Imidazolylidene-Iridium Complexation
Tran, Ngan; Department of Chemistry
This thesis describes the synthesis and use of an N– based proline–derived directing group towards the Birch reduction, diastereoselective alkylation, and the synthesis of NHC–iridium complexes that are precursors for the study of intramolecular aryl C–H activation. A pair of ortho–benzoate esters containing epimeric pyrroloimidazolone chiral auxiliaries underwent sequential Birch reduction and diastereoselective alkylation to provide products ranging from a 50:50 to 95:5 dr for the anti– epimer, and 88:12 to >95:5 diastereomeric ratio (dr) for the syn– epimer. Single crystal X–ray analysis of key anti–epimer–derived products, along with the comparison of the optical rotation measurements of enantiomers that were prepared from the syn–or anti– starting materials to its known enantiomer confirmed the stereoselectivity of the products. This work includes related Schultz stereoselective Birch reduction alkylation of anisole with a chiral benzamide except that the pyrroloimidazolone replaces the achiral methoxy group and serves as the stereodetermining element. In addition, the synthesis and evaluation of the N–phenyl iridium complex derived from the annulated aminal with syn–stereochemistry in the backbone was achieved. Exposure of the neutral Ir–complexes to anionic nucleophiles such as MeLi resulted in an increase of electron density at the Ir atom that initiated C–H bond activation. Lastly, a N–heterocyclic carbene ligand derived from the N–benzyl analogue of the auxiliary was also investigated. Attempts to design a monodentate ligand as well as a bidentate ligand bearing an alcohol side chain were both shown to be unsuccessful at this time.
Open Access
Development of Universal Biosensing Platforms Based on CRISPR/Cas12a systems
Li, Yongya; Department of Chemistry
CRISPR/Cas technologies possess the promising potential to affect biosensing field by providing a sensitive, precise, rapid, versatile and cost-effective method for diverse target detections. This thesis focusses on the development of CRISP/Cas12a based biosensing platforms for nucleic acid and protein detection. Two distinct CRISPR/Cas based diagnostic methods were developed. The first developed method is a plasmonic CRISPR Cas12a assay for colorimetric detection of viral nucleic acid. This assay generates colorimetric signals for nucleic acid amplicons by combining the unique target-induced collateral cleavage activity of Cas12a with plasmon coupling of DNA functionalized gold nanoparticles. The practical applications of this assay were successfully demonstrated through the nucleic acid detection of hepatitis B virus (HBV) and Grapevine Red-Blotch Virus (GRBV). The second developed method is a universal proximity CRISPR Cas12a assay for ultrasensitive detection of nucleic acids and proteins. The target recognition is achieved through proximity binding rather than direct CRISPR/Cas 12a recognition, allows the flexible assay design and expansion to target diverse targets. This assay was successfully adapted to detect nucleic acids and antibodies in both buffer and diluted human serum.
Open Access
Synthesis of Heteroleptic Redox-active and Spin-crossover Complexes
Pelaccia, Mark; Department of Chemistry
The following research regarding heteroleptic redox-active complexes with the potential for spin-crossover is synthetic in nature. The intent behind incorporating the Schiff base ligand N-(8-quinolyl)salicylaldimine with some redox-active species into a mixed ligand complex featuring a d4-d7 metal ion center was to prime the material for spin-crossover based on strong intermolecular interactions that would enhance cooperativity of the system. Single component systems that display spin-crossover behaviour paired with other physical properties like electrical conductivity hold significance in the field of multifunctional materials, of which there are few examples that feature mixed ligand systems. Information describing this type of chemistry and the magnetic interactions that govern these characteristics is introduced in the first chapter of this work. The synthetic strategies toward mixed ligand complexes in the form of [(Qsal)Fe(RAL)]+X- and [(Qsal)Co(RAL)]+X- have been realized from the use of mononuclear [(Qsal)FeCl2(CH3OH)] and [(Qsal)Co(OAc)]+OAc- species, respectively. The redox-active ligand (RAL) component is an arylazo ligand like 10-(8-quinolylazo)-9-phenanthrol (Qapl) or 1-(2-Pyridylazo)-2-phenanthrol (Papl), which possess a low-lying π* MO that makes them susceptible to multi-step reductions that give rise to radical intermediates. Heteroleptic complexes that were synthesized and isolated like [(Qsal)Fe(Qapl)]+BPh4-, [(Cl-Qsal)Fe(Qapl)]+BPh4-- and homoleptic [Fe(Qapl)2]+BPh4- were diffracted and measured several intermolecular π-π contacts of distances typically between 3.5-3.7 Å, often between the phenanthrene rings of adjacent Qapl ligands. Complexes In the form of [(Qsal)Fe(Qapl)]+X (X= BPh4- or SCN-) showed early onset of spin transition in solution usually beyond 298 K. These complexes were overly reduced in the glovebox which resulted in their deterioration, presumably from the cleavage of the RAL azo bond. The framework developed for the heteroleptic Fe3+ coordination chemistry was applied to cobalt, with some amendments, and afforded several heterleoptic Co3+ complexes using Qsal with the arylazo ligands Qapl and Papl. The heteroleptic cobalt complexes presented here were found to be LS Co3+ which is diamagnetic. However, there is potential under inert atmosphere to produce Co2+ and possibly a phenoxyl radical species with redox-active valence tautomers.
Open Access
Epimeric L-Proline Derived Imidazolone Chiral Auxiliaries for the Stereoselective Alkylative Birch Reduction of Aromatic Esters and Benzonitriles
Cadwallader, Dusty; Department of Chemistry
Described in this thesis are several advancements of imidazolidinone chiral auxiliaries. Initially, attempts were made to develop a N-heterocyclic carbene ligand derived from the N-benzyl analog of the auxiliary. Attempts to design a monodentate ligand as well as a bidentate ligand bearing an alcohol side chain were both shown to be unsuccessful. Work on the N-phenyl variant of the auxiliary included expanding upon our recently discovered methodology; a Birch reduction alkylation sequence of an aromatic ester yielding chiral quaternary carbon centres in a stereoselective matter. In substrates that demonstrate poor stereoselectivity, modification of the auxiliary to include a larger neopentoxy directing group gives way to increased selectivity. This work also includes the same Birch reduction alkylation sequence on a series of benzonitrile substrates with up to 64:36 diastereomeric ratio from either epimer of the auxiliary. The low selectivity of the benzonitrile substrates is offset by the resulting diastereomers of the dihydrobenzonitrile products being chromatographically separable. This results in the first preparation of optically pure quaternary carbons alpha to nitrile by Birch-type reductive alkylation. Progress was also made in the manipulation of chiral auxiliaries bearing the chiral alkoxy moiety. These functional groups were transformed into hemiaminals by citric acid hydrolysis in a 3:2 ratio with imidazolone by-products formed by acid mediated elimination of alcohol.
Open Access
The Synthesis of Phosphatidylinositol Bolalipids
Jewell, Shannon; Department of Chemistry
This thesis describes the attempted synthesis of phosphatidylinositol bolalipids to be used in the investigation of the mechanism of the phosphatidyl inositol transfer protein, Sec14, and the PI(4)-kinase, Pik1. The synthesis of two unique bolalipids was the goal of this thesis. The esterification of the sn1 position of a protected glycerol unit to stearic acid as well as esterification at the sn2 position to either the C20 or C36 diacid gave the framework of the desired bolalipid. Further success was seen in the coupling of benzyloxybis(diisopropylamino) phosphine to the sn3 position of the deprotected glycerol unit in the generation of a phosphoramidite. However, efforts in the final step of the synthetic method were unsuccessful and did not lead to the complete synthesis of the bola-PI. Though it was possible to couple the 2,3,4,5,6-benzyl protected myo- inositol to the phosphoramidite, the most significant issues in the synthesis of the bola-PI is the oxidation of the phosphite to the phosphonate. Despite multiple attempts with varying oxidizing agents, no oxidation was observed by TLC, P NMR or mass spectrometry data. Two phosphoramidites, precursors to the desired bola-PI molecules, have been synthesized to date. The two phosphoramidites were characterized by H NMR, C NMR, P NMR, mass spectrometry, and optical activity. They are both air and water sensitive and have been observed to decompose with storage, even when placed under nitrogen at -4 oC. Spectral and experimental data are provided for all new compounds.

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