Thesis (Ph. D.)--Rutgers University, 2010. / "Graduate Program in Food Science." Includes bibliographical references (p. 130-152).

Submitted by Geyciane Santos (geyciane_thamires@hotmail.com) on 2015-10-06T15:45:47Z No. of bitstreams: 1 Dissertação - Willian Hayasida.pdf: 5982366 bytes, checksum: 115e6b5fa82146b72ffe5d3c1be0554c (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-10-06T19:33:00Z (GMT) No. of bitstreams: 1 Dissertação - Willian Hayasida.pdf: 5982366 bytes, checksum: 115e6b5fa82146b72ffe5d3c1be0554c (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-10-06T19:47:15Z (GMT) No. of bitstreams: 1 Dissertação - Willian Hayasida.pdf: 5982366 bytes, checksum: 115e6b5fa82146b72ffe5d3c1be0554c (MD5) / Made available in DSpace on 2015-10-06T19:47:15Z (GMT). No. of bitstreams: 1 Dissertação - Willian Hayasida.pdf: 5982366 bytes, checksum: 115e6b5fa82146b72ffe5d3c1be0554c (MD5) Previous issue date: 2015-08-21 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / Wood is a material of natural origin widely used in several industrial sectors, formed by chemical compounds that usually are not considered during processing, particularly the secondary metabolites that consequently are rejected. In this study were evaluated wood residues of "louro-preto" (Ocotea cymbarum, Lauraceae), "tatajuba" (Bagassa guianensis, Moraceae) and "peãozinho" (Eschweleira coriaceae, Lecythidaceae), generated from the manufacture of parts of musical instruments and civil construction, to obtain knowledge of the secondary metabolites and aggregate value to solid residues. Therefore, the crude extracts were subjected to chromatographic fractionation in open column using as supports, silica gel, microcrystalline cellulose, Sephadex LH-20. The compounds obtained had the structure determination based on spectrometric and spectroscopic techniques. In residues from O. cymbarum hexane extract were identified the β-sitosterol and lignoceric acid; in the methanol extract was identified by HR-MAS the amino acid tyrosine. The hexane extract from E. coriaceae sapwood gave the triterpene lupeol and β-sitosterol and sitostenone steroids. In methanol extract of this species were identified phenanthrene micandrol A from sapwood and the micandrol B from heartwood. In the hexane extract of B. guianensis was detected the β-sitosterol and lupeol; the methanolic extract gave eight compounds identified as 2,4- dihydroxybenzaldehyde, trans-oxyresveratrol, kaempferol, stoppogenin, 6-O-methylmoracin N, moracin R 4'-O-a-xylopyranose and the moracins M and P. / A madeira é um material de origem natural amplamente utilizado em diversos setores industriais, formado por componentes químicos que usualmente não são considerados durante o seu processamento, principalmente os metabólitos secundários que por consequência acabam rejeitados. Neste trabalho avaliaram-se os resíduos madeireiros de louro-preto (Ocotea cymbarum, Lauraceae), tatajuba (Bagassa guianensis, Moraceae) e peãozinho (Eschweleira coriaceae, Lecythidaceae), proveniente da indústria de confecção de peças de instrumentos musicais e da construção civil, visando o conhecimento dos metabólitos secundários e agregação de valores aos resíduos sólidos. Dessa forma, os extratos brutos foram submetidos à fracionamentos cromatográficos em coluna aberta utilizando-se como suportes sílica gel, celulose microcristalina, Sephadex LH-20. As substâncias obtidas tiveram a determinação estrutural baseada em técnicas espectrométricas e espectroscópicas. Nos resíduos de O. cymbarum, identificou-se no extrato hexânico, o esteróide β-sitosterol e ácido lignocérico; no extrato metanólico foi identificado o aminoácido tirosina utilizando uma sonda HR-MAS. De E. coriaceae identificou-se no extrato hexânico do alburno, o triterpeno lupeol e os esteróides β-sitosterol e sitostenona. No extrato metanólico desta espécie foram identificados os fenantreno micandrol A do alburno e micandrol B do cerne. No extrato hexânico de B. guianensis detectou-se a presença de β-sitosterol e lupeol; no extrato metanólico obteveram-se oito substâncias, identificadas como 2,4-dihidroxibenzaldeído, transoxiresveratrol, canferol, estopogenina, 6-O-metil-moracina N, moracinas M e P, e moracina R 4’-O-a-xilopiranose, sendo está ultima inédita na literatura.

Resveratrol is a naturally occurring phytoalexin of the stilbene family produced by various plants in response to stress, UV radiation, and fungal attack. It is primarily found in peanuts, berries, grape skin, and red wine. Resveratrol has been found to exhibit anti-cancer, anti-inflammatory, anti-aging, and anti-oxidant properties. Research indicates that diets enriched with resveratrol containing substances result in less incidence of cancer. Unfortunately, the low bioavailability and solubility has been a huge setback for its potential prospects. As a result, efforts have been made to synthesize derivatives of resveratrol with increased solubility and bioavailability. Three triester novel resveratrol derivatives 3, 4’, 5-tri (benzoyloxy) stilbene, 3, 4’, 5-tri (toluyloxy) stilbene and 3, 4’, 5-tri (2”-butenoyloxy) stilbene have been synthesized by esterification process that can further be subjected for biological evaluation. Structures and purities of all newly synthesized derivatives were confirmed by 1H, 13C NMR spectroscopy and infrared spectroscopy.

The research in this dissertation is focused on the synthesis and characterization of sterically crowded, precisely charged polyelectrolytes based on substituted stilbene comonomers. New sterically crowded polyelectrolytes based on functionalized stilbenes with maleic anhydride or functionalized N-phenylmaleimides were prepared via a "protected" precursor polymer strategy. The polyelectrolyte precursors readily dissolved in organic solvents and were characterized by 1H NMR, SEC, TGA, and DSC. The polyelectrolytes were obtained via simple deprotection chemistries. The use of different combinations of the donor-acceptor comonomer pairs and the alternating copolymerization of these comonomers lead to precise control over charge density and placement of charged groups along the polymer backbone. Analogous styrenic copolymers, for direct comparison to the stilbene structures, were also prepared. Broad peaks in 1H NMR spectra were observed. There were no thermal transitions measured by DSC below the degradation temperature. A strong polyelectrolyte effect, for both stilbene and styrene copolymers, occurred in deionized water and was suppressed by adding NaCl to the polymer solution. These results are not consistent with "rigid" rod polyelectrolytes in which chain collapse in the presence of added salt and chain expansion on dilution should not be observed. In response to these observations persistence length measurements were conducted on the stilbene and styrene copolymers to assess directly the steric crowding effect of added phenyl groups in stilbene copolymers. Both SEC and SAXS measurements were used to obtain persistence lengths. The results from three different approaches, Bohdanecký, graphical and Sharp and Bloomfield Global, were in good agreement. The persistence lengths of stilbene containing copolymers range from 3 to 6 nm and the added phenyl groups increase the rigidity of the polymer chain by about 30-50%. This puts these polymers into a broadly defined "semi-rigid" category of polymers and is consistent with the solution polyelectrolyte effect observed. In dilute solution characterization of stilbene containing polyanions, a 2-step dissociation behavior was observed for the two adjacent carboxylic acids in maleic acid containing polyanions. Stilbene polyanion solutions showed high Rh values in deionized water as shown by DLS measurements and a decrease of Rh values followed by aggregation upon gradual addition of salt. Bimodal peaks were observed in SEC measurements with the copolymer of 4-methylstilbene and maleic anhydride. DLS measurements indicated interchain aggregation as the origin of the apparent high molecular weight fraction. The antiviral activity of the polyanion based on sodium 4-styrenesulfonate and N-(4-sodium sulfophenyl)maleimide was found to be ~50 times higher than the microbicide, sodium poly(styrene sulfonate). The early study of antiviral activities of carboxylated stilbene and styrene polyanions also showed promising results. The synthesis of methyl sulfonate ester-functionalized polyanion precursors was attempted because they can be characterized without the complications caused by directly using charged sulfonate groups. / Ph. D.

Ce travail de thèse porte sur le développement de techniques de spectroscopie neutronique dans les champs de rayonnement mixte pour des applications liées aux réacteurs de recherche à neutrons rapides, en particulier l’installation MASURCA.La première partie est consacrée à l'étude des configurations expérimentales spéciales de MASURCA dans lesquelles un canal radial est construit pour extraire un faisceau continu de neutrons d'énergie intermédiaires et rapides, adaptable à différents besoins. Exploiter MASURCA en tant qu'installation de faisceau de neutrons ouvrirait de nouvelles possibilités d'expériences telles que des expériences de protection et de transport de neutrons rapides, la production de champs neutroniques standards (de référence), le développement et étalonnage de systèmes de détection des neutrons rapides, etc.La deuxième partie de la thèse est dédiée au développement d’une capacité de spectrométrie neutronique rapide pour la caractérisation en ligne de la distribution d'énergie neutronique. Différents types de détecteurs sont comparés. Le meilleur compromis pour ce spectromètre est un système combinant des compteurs proportionnels et des scintillateurs organiques. Ce système est capable de couvrir le domaine énergétique entre 10 keV et 10 MeV. Le scintillateur organique sélectionné est un monocristal de stilbène obtenu par un procédé “solution-grown” développé récemment. Au bilan, on conclut qu'un spectromètre à neutrons basé sur le stilbène de type “solution-grown” serait adapté à une utilisation dans MASURCA et dans d'autres champs de rayonnement mixte et qu'il serait plus performant que les systèmes de détection traditionnels. / This doctoral thesis work is focused on the development of neutron spectroscopy techniques in mixed radiations fields for fast research reactor applications, especially for the MASURCA facility.The first part of the thesis is dedicated to the study of special MASURCA configurations in which a radial channel is built to extract a continuous beam of intermediate-to-fast energy neutrons, tailorable to meet different needs. Operating MASURCA as a neutron beam facility would open up new possibilities of experiments, such as fast neutron attenuation and shielding experiments; measurements in standard (reference) fast neutron fields, development and calibration of fast neutron detection systems etc.The second part of the thesis is dedicated to the development of fast neutron spectrometric capabilities for the on-line characterization of the neutron energy distribution. Different candidate detector systems are compared. A “best compromise” spectrometer is shown to be a system combining proportional counters and organic scintillators. Such a system would be able to cover the neutron energy domain between 10 keV and 10 MeV. The selected organic scintillator is a stilbene single crystal obtained by a recently developed solution-grown process. Overall, it is concluded that a neutron spectrometer based on a solution-grown stilbene detector would be suitable for use in MASURCA and in other mixed radiations fields, and would perform better than traditional detector systems.

Die Relaxation der Styrylfarbstoffe DCM und LDS-750 nach Photoanregung in flüssiger Phase wurde mittels zeitaufgelöster optischer Spektroskopie untersucht. Dabei wurde die Breitband-Pump-Probe-Technik angewandt. Zur Charakterisierung der Relaxation von DCM im elektronischen Grundzustand wurde außerdem die Breitband-Dump-Probe-Technik (stimuliertes Emissionspumpen) eingesetzt. Für die beobachtete schnelle Relaxation von DCM wurde eine annähernd lösungsmittelunabhängige Zeitkonstante von 0.23 (( 0.04) ps im elektronisch angeregten und von 0.28 (( 0.07 ps) im elektronischen Grundzustand gefunden. Sie wurde als Konforma tionsänderung mit nur geringer Ladungsverschiebung charakterisiert. Die weitere spektrale Entwicklung wird in polarer Lösungsmittelumgebung vorwiegend von der Solvatation bestimmt. Für das ionische Polymethin LDS-750 wurden nach der Anregung solvensabhängige Kinetiken beobachtet, die sich durch die Annahme dreier möglicher Konformationen im S1 erklären lassen. / Relaxation of the stryryl dyes DCM and LDS-750 after photoexcitation in the liquid phase has been investigated by means of time-resolved optical spectroscopy. For this purpose, the broadband pump-probe technique was used. To characterize the relaxation of DCM in the electronic ground state, additionally the broadband dump-probe technique (stimulated emission pumping) was applied. An approximately solvent-independent time constant was found typical for the observed fast relaxation of DCM, with values of 0.23 ((0.04) ps in the excited and 0.28 (( 0.07 ps) in the electronic ground state. The relaxation was characterized as conformational change with only a small amount of charge transferred. The further spectral evolution in polar solvents was dominated by solvation dynamics.For the ionic polymethine species LDS-750 solvent-dependent kinetics were found after photoexcitation. They could be accounted for by assuming the existence of three different conformers within the S1 state.

La maladie de Parkinson est l’une des plus répandue dans le monde. Des analyses post mortem ont mis en évidences des inclusions dans les cerveaux des patients, composées d’α-synucléine. Plusieurs études ont visé à identifier des composés capables d’inhiber l’agrégation de cette protéine, étant donné que cette agrégation est liée à sa toxicité. Néanmoins, de nombreux composés restent encore à être identifiés afin de mettre en évidence des structures moléculaires actives partagées qui pourrait mener à la synthèse d’un principe actif. Les stilbènes sont des composés phénoliques démontrant régulièrement des activités biologiques intéressantes pour la santé. Dans cette étude, nous étudions le comportement anti-agrégatif des stilbènes monomériques (resvératrol, picéatannol) et oligomèriques (ampélopsine, viniférine, et isohopeaphénol). Les résultats présentés mettent en évidence la capacité des stilbènes à inhiber l’agrégation de l’α-synucléine et fournissent des éléments pour comprendre ce mécanisme. / Parkinson’s disease is one of the most spread neurodegenerative diseases in the world. Post mortem analyses have put in evidence small inclusion bodies in patient’s brain, composed of α-synuclein fibrils. Several studies attempted then to identify compounds that could inhibit α-synuclein aggregation, as its aggregation is linked to its toxicity. Still, numerous active compounds need to be identified in order to put on relief shared active structures that could lead to a potent drug design. Stilbenes are phenolic compounds that often display interesting health-related biological activities. In this study, the anti-aggregative behavior of stilbenes monomers (resveratrol, piceatannol) and oligomers such as ampelopsin and isohopeaphenol was assessed. The results put on evidence stilbene propensity to inhibit α-synuclein aggregation and provide an insight into their inhibition mechanisms.

£¸¡B Pyrolysis of 2-methoxy-2¡¦-methylthiostilbene (22a) and 2,2¡¦-di(methylthio)stilbene (22b) gave not only polycyclic aromatic hydrocarbons (PAH) 17¡B18¡B2, but also the products 33, 34. In addition, photolysis of 22a¡B22b¡B2,2¡¦-dimethoxy stilbene (13) gave photocyclic products 31¡B40¡B12¡B45¡B46. ¤G¡B Pyrolysis of 2-dimethylamino-N-(arenylidene)anilines (20a-f) gave not only 1-methyl-2-arylbenzimidazole (25a-f), but also gave 2-arylquinoxaline (26a-e). Furthermore, compound 20f gave 37 and 25f, but didn't give 26f. ¤T¡B Pyrolysis of benzoic 1,2-dimethyl-3-indolyl anhydride gave 1,2-dimethylindole (19) ¡B3-methylquinoline (30) ¡B4-methylquinoline (31).

Stilbenoids possess a wide range of biological properties such as, anticancer, antiplatelet aggregation, antiestrogenic, antibacterial, antifungal and antiatherogenic, etc. Owing to these therapeutic values, a great deal of attention attracted in the synthesis of derivatives of stilbenes. During the course of the study, G6 a novel stilbenoid was discovered, through high throughput screening, to be a potent inhibitor of mutated JAK2-V617F. The mutated JAK2 variant has been implicated in various myeloproliferative disorders (MPDs) including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) has been targeted by therapeutics. Chapter 2 describes the synthesis of analogs of the stilbenoid G6 and N-substituted stilbenes bisoxazines by utilizing Mcmurry reaction and Mannich condensation methods. The main emphasis of this work is to develop novel stilbenoids as inhibitors of JAK2-V617F mutated Jak2 enzyme in Human erythroleukemia cells (HEL) since this mutation is discovered in the majority of patients with myeloproliferative disorders (MPDs). Using Mcmurry reaction, five novel trans-hydroxystilbenes have been synthesized from carbonyl compounds. Subsequently using Mannich coupling with five secondary amines and five primary amines, 25 novel stilbenoids and 9 novel N-substituted stilbene bisoxazines have been synthesized. In HEL cell assay, 8 stilbenoid analogues have been identified as potent inhibitors of Jak2 enzyme. Chapter 3 describes the modification of ketamine structurally for the synthesis of novel analogues to study for their agonist activity at GABAA receptors and antagonist activity at NMDA receptors. Ligand gated ion channels like GABAA and NMDA receptors are membrane-embedded proteins at synaptic cleft which controls intercommunication among neurons and plays an important role in motor control activity, learning. GABAA receptors are responsible for inhibitory action potentials while NMDA receptors are responsible for excitory action potentials. Ketamine, known as dissociative anesthetic, produces profound analgesia at low doses to a unique cardiovascular stimulation and a cataleptic state at higher doses with dose dependent side effects like vivid dreams, disruptions of cognitive functions. The main emphasis of this work is the synthesis of novel analogues of ketamine by transforming carbonyl group in ketamine to imine functionality with small to bulkier groups and to identify an analogue of ketamine which is highly potent in its activity at the both GABAA and NMDA receptors and improved clinical actions. Studies of analogues activity against GABAA subtypes α6Β2δ, α1Β2γ2 receptors and NMDA subtypes NR1/2A, NR1/2B, NR1/2D receptors have been described. Chapter 4 describes the formal synthesis of (±)-Rolipram and the chemoenzymatic synthesis of -aryl--lactone, a Rolipram analogue. The key steps, Pd catalyzed arylation of diethylmalonate and the efficient use of selective acylation of 1, 3-diol entails the formal synthesis of (±)-Rolipram. The regioselective deacylation of Β-aryl-1, 4-diacetate by lipase Pseudomonas Sepacia entails the formation of Β-aryl-γ-lactone. The efficient use of various methods including halogen exchange, Heck arylation of diethylmaleate and lactonization for the synthesis of Β-aryl-γ-lactone have been discussed. The present work provides an efficient and general route to γ-lactones.

Le bois est un matériau renouvelable utilisé par l’Homme pour la construction, l’ameublement, la fabrication du papier, l’énergie, etc. Le bois contient des extractibles d’un grand intérêt économique appartenant à diverses familles chimiques telles que les terpènes, les flavonoïdes, les tanins, etc. Les nœuds (base de la branche englobée dans le tronc) de certaines essences sont extrêmement riches en extractibles.Ce travail a pour objectif l’analyse des variabilités interspécifiques, intraspécifiques et intra-arbre des extractibles nodaux, afin de cibler les essences, les stations et les parties de l’arbre les plus riches. Pour cela, les nœuds de vingt-trois essences, puis ceux de quinze sapins ayant poussé dans des conditions différentes ont été extraits par différents solvants et analysés. Les résultats confirment la richesse des nœuds par rapport au duramen et à l’aubier pour toutes les essences. Globalement, les nœuds des résineux contiennent plus d’extractibles que les feuillus. Les principaux composés identifiés chez les résineux sont des lignanes, des stilbènes, des flavonoïdes et des terpènes. L’acide gallique et des flavonoïdes sont présents chez les feuillus. L’étude du profil vertical montre que les concentrations diminuent de la base du houppier vers la cime de l’arbre. De plus, les résultats mettent en évidence l’influence des conditions de croissance puisque les arbres dominants, et/ou ayant poussé selon des sylvicultures dynamiques sont particulièrement riches en extractibles nodaux. Ces résultats permettent d’envisager la valorisation des coproduits des industries du bois en tant que ressource de molécules bioactives pour diverses applications. / Wood is a renewable material used by man for construction, furniture, paper making, energy, etc. Wood contains extractives of great economic value which belong to various chemical families such as terpenes, flavonoids, tannins, etc. The knots (base of the branch embedded in the trunk) of some tree species are extremely rich in extractives.This study aims at analysing the inter-specific, intra-specific and within-tree variabilities of knotwood extractives to target the richest species, stations and tree parts. For that purpose, the knots of twenty-three species and those of fifteen firs grown under different conditions were extracted using several solvents and analysed. The results confirm the richness of knots compared to heartwood and sapwood for all species. Overall softwood knots contain mainly more extractives than hardwoods. The main compounds identified in softwoods are lignans, stilbenes, flavonoids and terpenes Gallic acid and flavonoids are present in hardwoods. The study of the vertical profile shows that concentrations decrease from the base of the crown to the tree tip. In addition, the results highlight the influence of growth conditions since dominant trees and/or those grown according to dynamic silvicultures are particularly rich in knot extractives. These results allow considering the valorization of wood industries by-products as bioactive molecules resource for various applications.