307,726 research outputs found
Syntheses of the enantiopure quinones A and A' and their C-1 epimers
No full textThe 3,4-dihydro-1H-naphtho[2,3-c]pyran ring system is found in many natural products as the 5,10- or 6,9-quinones. These compounds have been synthesized by various research groups as a result of their wide range of biological activities. This thesis describes several investigations directed towards syntheses of compounds in this general area. Quinone A (16) and quinone A'(17), derived from the naturally occurring aphid insect pigments protoaphin-fb and protoaphin-sl respectively, were of particular interest.
The first chapter describes the previous syntheses of some naphtho[c]pyrans including those relating to the aphid pigment derivatives, followed by the isolation and identification of the aphid pigments. Also described was the ability of these naphthopyranquinones to act as potential bioreductive alkylating or dealkylating agents. The latter part of the chapter deals with the syntheses of the racemates of the aphid pigment derivatives quinones A and A' and deoxyquinone as well as model studies toward the non-quinonoid cleavage product, glucoside B. The chapter concludes with the progress made towards the first asymmetric synthesis of these compounds.
Chapter 2 reports the establishment of conditions which led to ortho or para regioselectivity in the intramolecular cyclisation of tethered lactaldehydes to form benzo[c]pyrans. This regioselectivity depended on whether either benzyl or tbutyldimethylsilyl was used as protecting group. This chapter also described a model for the control of stereochemistry leading to quinone A'.
Chapter 3 describes the syntheses of naphthalenes as potential precursors to the naphthopyranquinones derived from the aphid insect pigments. This followed after problems were encountered in previous work with inappropriate protection in the oxidation of halogenated benzopyrans.
Chapter 4 develops the first successful syntheses of enantiopure quinone A and quinine A' with the correct absolute stereochemistry. This involved the regioselective addition of 1,3-bis(trimethylsilyloxy)-1-methoxybuta-1,3-diene toselectively halogenated benzopyranquinones. The latter were obtained through complementary series of highly diastereoselective transformations based on 2,5- dihydroxyacetophenone as starting material and (R)-lactate from the chiral pool as the source of asymmetry
A search for shorter, more convergent routes to enantiopure naphthopyrans related to the aphid insect pigments
No full textThe naphtho[2,3-c]pyran ring system is generally found amongst natural products as the 5,10- or 6,9-quinones. These compounds display a wide range of biological activities, and as such, have been synthesised by various research groups. The synthetic work described in this thesis is directed towards finding shorter, more convergent routes to enantiopure quinone A 10, quinone A' 11 and quinone-pm 13, three derivatives of the aphid insect pigments protoaphin-fb 6, protoaphin-sl 7 and protoaphin-pm 9, respectively.
The first chapter describes the previous syntheses of some naphtho[2,3-c]pyrans including those relating to the aphid insect pigment derivatives. Also detailed is the ability of these naphthopyranquinones to act as potential bioreductive alkylating and dialkylating agents. The latter part of the chapter records some of the previously achieved assemblies of quinones A 10 and A' 11 in both racemic and enantiopure form, as well as the only synthesis of enantiopure quinone-pm 13.
Chapter 2 involves the preparation of regioselectively halogenated aryldioxolanes starting with the allylation of brominated and chlorinated phenols. The isomerisation of these dioxolanes into the corresponding halogenated 2-benzopyrans is then investigated.
Chapter 3 examines the regioselectivity of the Diels-Alder reaction between protected benzopyranquinones and the substituted diene 1-methoxy-1,3-bis(trimethylsilyloxy)-buta-1,3-diene 80. Such protection involves preparing the acetates and methoxymethyl ethers of the benzopyranquinones. The latter part of the chapter describes the direct bromination of benzopyranquinones.
Chapter 4 reports on the stereoselective reaction between metal phenolates and the chiral aldehyde 108 to subsequently afford naphthyldioxolanes 264, 291, 292 and 295. The rearrangement reaction of the derived naphthyldioxolane 295 is then investigated
Quinones as Neuroprotective Agents
No full textQuinones can in principle be viewed as a double-edged sword in the treatment of neurodegenerative diseases, since they are often cytoprotective but can also be cytotoxic due to covalent and redox modification of biomolecules. Nevertheless, low doses of moderately electrophilic quinones are generally cytoprotective, mainly due to their ability to activate the Keap1/Nrf2 pathway and thus induce the expression of detoxifying enzymes. Some natural quinones have relevant roles in important physiological processes. One of them is coenzyme Q10, which takes part in the oxidative phosphorylation processes involved in cell energy production, as a proton and electron carrier in the mitochondrial respiratory chain, and shows neuroprotective effects relevant to Alzheimer’s and Parkinson’s diseases. Additional neuroprotective quinones that can be regarded as coenzyme Q10 analogues are idobenone, mitoquinone and plastoquinone. Other endogenous quinones with neuroprotective activities include tocopherol-derived quinones, most notably vatiquinone, and vitamin K. A final group of non-endogenous quinones with neuroprotective activity is discussed, comprising embelin, APX-3330, cannabinoid-derived quinones, asterriquinones and other indolylquinones, pyrroloquinolinequinone and its analogues, geldanamycin and its analogues, rifampicin quinone, memoquin and a number of hybrid structures combining quinones with amino acids, cholinesterase inhibitors and non-steroidal anti-inflammatory drugs.Ministerio de Ciencia e InnovaciónDepto. de Química en Ciencias FarmacéuticasTRUEpubDescuento UC
OpenMP runtime
No full textThis chapter introduces the design of the OpenMP runtime and its key components, the offloading library and the tasking runtime library. Starting from the execution model introduced in the previous chapters, we first abstractly describe the main interactions among the main actors involved in program execution. Then we focus on the optimized design of the offloading library and the tasking runtime library, followed by their performance characterization
Preface [Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)]
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The Synthesis and Reactivity of Vitamin E Quinones
No full textVitamin E has been the subject of numerous studies over the last nine decades since its discovery. Still, the biological activity of vitamin E is not completely understood. Various studies suggest that the primary function of vitamin E is a fat-soluble antioxidant preventing lipid peroxidation in cellular membranes. The antioxidant efficiency across the vitamin E isomers have been shown to be similar in vitro in various organic solvents and aqueous lipid suspensions. Despite these results, significantly different biological effects have been observed in biological assays supplemented with the various tocols. Furthermore, the differences are more pronounced when comparing the biological effects of the α-tocols to non α-tocols. We hypothesized the different biological effects observed were correlated to differences in the chemical reactivity of the products of tocol oxidation: tocol quinones. Herein, an investigation of the adduct formation of tocol quinones with N-acetyl cysteine (NAC) is described.
The synthesis of the tocopheryl quinones is described via the two-electron oxidation of the parent tocols with ceric ammonium nitrate supported on silica. The synthesis of α-tocopherol quinone and α-tocotrienol quinone produced the target compounds in 80% yield. The oxidations of the other tocol isoforms yielded para-tocol quinones (29-45% yield) and ortho-tocol quinones (20-35% yield). The rate of reaction of the tocopheryl quinones with NAC was monitored by following the production of the tocopherol hydroquinone adduct by the increase in absorption at 308 nm over time in a 67% methanol/ 33% aqueous Tris/HCl buffer. The curves generated were fit to a one-phase exponential. The rate of reaction increased as the pH increased for the γ- and δ-tocopheryl quinone isoforms. There was no reactivity observed between the α-tocopheryl quinone isoforms and NAC. There was no significant difference in the reactivity between the tocopherol quinones and tocotrienol quinones with the same methylation pattern. At the most physiologically relevant pH in our study (pH = 7.5), the δ-tocopheryl quinones (k ≈ 0.63) reacted approximately 8 times faster than the γ-tocopheryl quinones (k ≈ 0.08). The electrochemistry of the parent tocols was studied using cyclic voltammetry (CV). The formal redox potential increased slightly as the methylation on the chromanol ring decreased while no significant differences between the tocopherols and tocotrienols were established. The CV of all tocols showed two quasi-reversible one-electron oxidation processes; the first oxidation produced a radical cation, which quickly deprotonated to form a tocopheryl radical, which then undergoes a second oxidation to the corresponding phenoxonium cation. The redox activity of the tocopheryl quinones was also studied using CV. The quinones underwent a quasi-reversible two one-electron reduction process. The δ-tocopheryl quinones have the lowest formal redox potential which slightly increases as methylation increases, while there were no significant differences in the electrochemical behavior of the tocopheryl quinones and the tocotrienyl quinones with the same methylation. We have presented reaction rate differences in the reactivity of the tocol quinones which correlates to the differences in biological activity observed by others with respect to the methylation pattern on the chromanol ring, while no differences in the chemical reactivity of the tocopherol and tocotrienol quinones was observed. Still, this presents convincing evidence that the activity of the tocol quinones should be considered in biological assays
The Pisum sativum SAD short-chain dehydrogenase/reductase: quinone reduction, tissue distribution, and heterologous expression
No full textThe pea (Pisum sativum) tetrameric short-chain alcohol dehydrogenase-like protein (SAD) family consists of at least three highly similar members (SAD-A, -B, and -C). According to mRNA data, environmental stimuli induce SAD expression (Brosché and Strid (1999) Plant Physiol 121: 479-487). The aim of this study was to characterize the SAD proteins by examining their catalytic function, distribution in pea, and induction in different tissues. In enzyme activity assays using a range of potential substrates, the SAD-C enzyme was shown to reduce one- or two-ring membered quinones lacking long hydrophobic hydrocarbon tails. Immunological assays using a specific antiserum against the protein, demonstrated that different tissues and cell types were shown to contain small amounts of SAD protein that was predominantly located within epidermal or sub-epidermal cells and around vascular tissue. Particularly high local concentrations were observed in the protoderm of the seed cotyledonary axis. Two bow-shaped rows of cells in the ovary and the placental surface facing the ovule also exhibited considerable SAD staining. UV-B irradiation led to increased staining in epidermal and sub-epidermal cells of leaves and stems. The different localization patterns of SAD suggest functions in both development and in responses to environmental stimuli. Finally, the pea SAD-C promoter was shown to confer heterologous wound-induced expression in Arabidopsis thaliana, which confirmed that the inducibility of its expression is regulated at the transcriptional level
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Emotional labour and burnout in the leisure industry: a comparison between Spain and the UK from a conservation of resources perspective
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
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