A new, efficient route was used in the synthesis of [2.2]-paracyclophane-2-carboxylic acid. The acid as then resolved and the Birch reduction performed yielding one enantiomer of tetrahydro-[2.2]-paracyclophane-2-carboxylic acid. The ultraviolet spectrum of tetrahydro-[2.2]-paracyclophane- 2-carboxylic acid in isopenthane shows one absorption at 206 nm (Emax = 5,271). There are three bands observed in the circular dichroism spectrum in isopentane at 236 nm ([] = 1.8 X 104), 201 nm ([0] = -16 X 104) and a positive band indicated below 180 nm but not observed. The bands were assigned and possible reasons for the occurrence of a mr'r* transition at unexpectedly long wavelengths are discussed.

The work presented in this dissertation revolves around the incorporation of t-butyl methacrylate into block copolymers utilizing anionic living polymerization techniques. The synthesis of t-butyl methacrylate/n-hexyl methacrylate and t-butyl methacrylate/2-ethylhexyl methacrylate di- and triblock copolymers was done by initiation with 2-methyl-1,1-diphenylpentyllithium in THF at -78°C by established techniques, and predictable molecular weights and narrow molecular weight distributions were obtained. Subsequent selective acid catalyzed hydrolysis of the t-butyl ester followed by neutralization with an appropriate base allowed the formation of block ioncontaining polymers. The synthesis of triblock polymers of t-butyl methacrylate with butadiene and styrene/butadiene systems and their analogous block ionomers was also carried out utilizing difunctional organolithium initiation of the hydrocarbon monomers in cyclohexane. For the polymerization of the tbma, it was found that the addition of large quantities of a polar solvent, such as THF, endcapping with diphenylethylene, and low temperatures (ca. -70 °C) were necessary to avoid side reactions which were theorized to be carbonyl attack by the dienyl- or styryllithium species. It was found that in the all methacrylic systems mentioned, when the t-butyl methacrylate blocks were in the ester form, i.e. not hydrolyzed to the acid or neutralized to the ionomer, the copolymers were phase mixed as evidenced by thermal analysis. Upon derivatization, however, the block polymers became phase separated. Morphological characterization of the block ionomers indicated that the morphology was dependent on both the ionic content and the ionic block length. Well defined, partially anisotropic, morphologies were observed by SAXS and TEM only in polymers that had both high ionic content and relatively large ionic block lengths. Elastomeric behavior was observed in copolymers with triblock architecture, but the materials degraded prior to plastic flow. On the other hand, all of the diene- and styrene/diene-methacrylates exhibited a multiphase morphology in the precursor state. Analogously to the all methacrylic system, the block ionomers were elastomeric, with the rubbery plateau extended ca. 60 °C relative to the non-ionic precursors. Crosslinking of the poly(butadiene) phase occurred at the onset of plastic flow, rendering the ionomers unable to be thermally processed. / The work presented in this dissertation revolves around the incorporation of t-butyl methacrylate into block copolymers utilizing anionic living polymerization techniques. The synthesis of t-butyl methacrylate/n-hexyl methacrylate and t-butyl methacrylate/2-ethylhexyl methacrylate di- and triblock copolymers was done by initiation with 2-methyl-1,1-diphenylpentyllithium in THF at -78°C by established techniques, and predictable molecular weights and narrow molecular weight distributions were obtained. Subsequent selective acid catalyzed hydrolysis of the t-butyl ester followed by neutralization with an appropriate base allowed the formation of block ioncontaining polymers. The synthesis of triblock polymers of t-butyl methacrylate with butadiene and styrene/butadiene systems and their analogous block ionomers was also carried out utilizing difunctional organolithium initiation of the hydrocarbon monomers in cyclohexane. For the polymerization of the tbma, it was found that the addition of large quantities of a polar solvent, such as THF, endcapping with diphenylethylene, and low temperatures (ca. -70 °C) were necessary to avoid side reactions which were theorized to be carbonyl attack by the dienyl- or styryllithium species. It was found that in the all methacrylic systems mentioned, when the t-butyl methacrylate blocks were in the ester form, i.e. not hydrolyzed to the acid or neutralized to the ionomer, the copolymers were phase mixed as evidenced by thermal analysis. Upon derivatization, however, the block polymers became phase separated. Morphological characterization of the block ionomers indicated that the morphology was dependent on both the ionic content and the ionic block length. Well defined, partially anisotropic, morphologies were observed by SAXS and TEM only in polymers that had both high ionic content and relatively large ionic block lengths. Elastomeric behavior was observed in copolymers with triblock architecture, but the materials degraded prior to plastic flow. On the other hand, all of the diene- and styrene/diene-methacrylates exhibited a multiphase morphology in the precursor state. Analogously to the all methacrylic system, the block ionomers were elastomeric, with the rubbery plateau extended ca. 60 °C relative to the non-ionic precursors. Crosslinking of the poly(butadiene) phase occurred at the onset of plastic flow, rendering the ionomers unable to be thermally processed. / Ph. D.

Proteins have been known for years as the most important constituent of living matter. Their great abundance in all forms of life have made them the subject of chemical and alchemical investigations since the dawn of science. It was found during the nineteenth century, however, that these relatively complex protein polymers could be decomposed by various means to form their monomers- the amino acids. This process, in fact, takes place during the digestion and ingestion of proteins as food matter. Today, the most important use of the amino acids is as a food. With the scarcity of food so prevalent throughout the world today, it would seem desirable to devise a means of synthesizing a foodstuff from ordinarily non-edible material. Glutamic acid, one of the more common amino acids, occurs to a large extent in any agricultural products, principally core, soy-beans and beet-sugar waste. In addition to its use as a food, the sodium salt of this compound-monosodium glutamate- is very widely used as a flavoring. Moreover, the pure acid has been found recently to have brain stimulating properties and to increase the intelligence of persons taking it medicinally. There are many methods known for the synthesis of this compound. But their disadvantage is that the starting materials are themselves often uncommon and costly items. It was thought from a study of the structure of the acid, that the glutamic acid molecule could be built up from relatively simple materials, since it is only a combination of carbon, water and ammonia. One of the most practical methods devised was first, the production of glutaric acid from propane, via chlorination, followed by the amination of glutaric acid to form the amino acid - glutamic acid. The purpose of this thesis, therefore, was to develop a practical method for the synthesis of glutamic acid, starting with propane, and through the processes of chlorination, nitrilization, hydrolysis and amination, producing this acid. It was further proposed to design a pilot plant for the further carrying out of this work. / Master of Science

Thirty-five volunteers were randomized and twenty-nine completed the study. Mean plasma and red blood cell (RBC) total DHA concentrations, which were analyzed among all participants as a measure of adherence, increased significantly in the DHA-enriched treatment compared to control oil-control flour. The plasma and RBC n-6: n-3 ratio was reduced after consumption of HOCODHA-control flour compared to control oil- control flour. The present study failed to see differences in body composition with the HOCODHA-barley flour treatment versus control oil-control flour treatment. In conclusion, significant increases in plasma EPA and DHA levels, as well as the omega-3 index, provide evidence supporting the cardioprotective effects of HOCODHA. The present study demonstrated that in the context of current Western macronutrient intakes, altering the dietary fatty acid composition and adding β-glucan had no major effect on body composition during the 28 days controlled dietary intervention. / February 2017

No description available.

Genetic code expansion allows the incorporation of non-canonical amino acids with a variety of new functional groups: fluorescent amino acids,1-3 azides,4-6 alkynes,5-10 and photocrosslinkers.4,11,12 This incorporation requires the evolution of new tRNA/aminoacyl tRNA sythetase pairs. Traditionally screenings of novel tRNA/aminoacyl tRNA synthetase pairs have been done in vivo. While these in vivo screenings have proven robust, they are limited in multiple ways: non-canonical amino acids (ncAAs) must be nontoxic and bioavailable. Furthermore, library size is limited by transformation efficiency. Lastly, in vivo screenings require substantial amounts of the target ncAA, which is often not available in large masses. In vitro screenings bypass these limitations: toxicity and bioavailibilty are no longer concerns. Library size can be expanded by several orders of magnitude as we are no longer limited by transformation efficiency. Lastly, because in vitro transcription/translation reactions are routinely conducted on the μL scale, ncAA usage can be minimized. We set out to use in vitro compartmentalization to further expand the code. In an in vitro compartmentalization screening, the water droplets in a water-in-oil emulsion serve as separate reaction chambers in which individual library members are transcribed and translated. Here we report optimization of S30 transcription/translation reactions. Optimizations include cell lysis method, reaction temperature, template amount, and T7 RNA polymerase amounts. Yields remained low and we transistioned into the use of PURExpress. Fluorohistidines are isosteric with histidine, but not isoelectronic.13 This change in environment results in a reduction of pKa. We set out to synthesize 4-fluorohistidine to use as a pH probe in several target proteins. A synthesis of 4-fluorohistidine was published in 1973.14,15 We were able to improve upon this synthesis by reducing cost and improving yield of a key step in the reaction. Next, small peptides with polyhistidine tags were translated in vitro using our 4-fluorohistidine. We are calling this polyhistidine tag incorporating 4-fluorohistidine our “hexafluorohistag.” Because of the reduced pKa of the 4-fluorohistidine, the hexafluorohistag showed affinity to Nickel-NTA resin even at reduced pH. This allowed for the purification of hexafluorohistagged peptides in the presence of traditional polyhistidine-tagged peptides.

Wan Leong Hang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 80-83). / Acknowledgments --- p.i / Bibliography --- p.ii / Contents --- p.iii / Abstract --- p.iv / Abbreviations --- p.v / Chapter I --- Introduction / Chapter I-1 --- General Background of Pseudo-sugar --- p.1 / Chapter I-2 --- Monocarba-sugar --- p.2 / Chapter I-3 --- Dicarba-sugar --- p.4 / Chapter I-4 --- Isolation of Valiolamine and Its Related Compounds --- p.6 / Chapter I-5 --- Previous Syntheses of Valiolamine --- p.8 / Chapter II --- Results and Discussions / Chapter II-1 --- General Strategy --- p.17 / Chapter II-2 --- "Synthesis of (lR,2R)-diol (62)" --- p.20 / Chapter II-3 --- Synthesis and Reactivity of Olefin 69 --- p.24 / Chapter II-4 --- "Synthesis of (1R,2S) and (lR,2R)-diastereoisomers 25 and 27" --- p.27 / Chapter II-5 --- "Synthesis of (1S,2R)-diastereoisomer 26 and Valiolamine" --- p.32 / Chapter II-6 --- "Comment on the Regio Chemistry of Nucleophilic Attack of 68, 65 and" --- p.85 / Chapter II-7 --- Results of Biological Test --- p.43 / Chapter III --- Conclusion --- p.46 / Chapter IV --- Experimental --- p.48 / Chapter V --- Reference --- p.80

Considering the major role of insulin signaling on fatty acid synthesis via stimulation of lipogenic enzymes, differential effects of insulin signaling on individual carbon fluxes for fatty acid synthesis have been investigated by comparing the individual lipogenic fluxes in WT and IRS-1 knockout (IRS-1 KO) brown adipocytes. Results from experiments on WT and IRS-1 KO cells incubated with [5-¹³C] glutamine were consistent with the existence of reductive carboxylation pathway. Analysis of isotopomer distribution of nine metabolites related to the lipogenic routes from glucose and glutamine in IRS-1 KO cells using [U-¹³C] glutamine as compared to that in WT cells indicated that flux through reductive carboxylation pathway was diminished while flux through conventional TCA cycle was stimulated due to absence of insulin signaling in IRS-1 KO cells. This observation was confirmed by quantitative estimation of individual lipogenic fluxes in IRS-1 KO cells and their comparison with fluxes in WT cells. Thus, these results suggest that glutamine’s substantial contribution to fatty acid synthesis can be directly manipulated by controlling the flux through reductive carboxylation of alpha-ketoglutarate to citrate using hormone (insulin). / Singapore-MIT Alliance (SMA)

The term "lipid" covers an extremely diverse range of chemical or molecular species. Lipids, defined as molecules that are sparingly soluble in water but readily soluble in organic solvents, are broadly categorized into "neutral " or "apolar" lipids, and "amphiphilic” or "polar" lipids. Neutral lipids will include simple hydrocarbons, carotenes, triacylglycerols, wax esters, sterol eaters, as wel1 as other lipids such as fatty acids, polyprenols, and sterols In which the hydrophilic function has little Impact on the overall molecular characteristics. Polar lipids include phospholipids, glycolipids, sulfolipids, some sphingolipids, oxygenated carotenoids and chlorophylls.

N-sec -butylthioloated β-lactam (NsβL) is a novel beta-lactam antimicrobial with a mechanism of action proposed to inhibit 3-oxoacyl-acyl carrier protein synthase (ACP) III (FabH), resulting in the inhibition of fatty acid synthesis. It has been suggested that NsβL inhibits FabH indirectly by inactivating coenzyme-A (CoA). CoA is an essential cofactor for numerous proteins involved in glycolysis, the citric acid cycle (TCA), and pyruvate metabolism, in addition to fatty acid biosynthesis. This study aimed to determine the effects of NsβL on a diverse array of laboratory and clinical Staphylococcus aureus isolates by analyzing the mode of resistance in spontaneous and adaptive mutant NsβL-resistant mutants. Phenotypic analysis of the mutants was performed, as well as sequence analysis of fabH; along with comparative proteomic analysis of intracellular proteomes. Our results indicate that NsβL resistance is mediated by drastic changes in the cell wall, oxidative stress response, virulence regulation, and those pathways associated with CoA. It is our conclusion that Nsβ L has activity towards CoA, resulting in wide-spread effects on metabolism, virulence factor production, stress response, and antimicrobial resistance.