This diploma thesis deals with macerates of comfrey (Symphytum officinale) in selected fats (food lard, cosmetic lard and almond oil). Selected fats were first characterized by dry matter content, saponification, acid, iodine number, peroxide value. At the same time, total and free fatty acids were determined using GC-FID. Macerates were prepared by extraction of comfrey roots with selected fats. In prepared macerates the change in acid and peroxide value was monitored, as well as the content of selected bioactive compounds. The content of total phytosterol and total carotenoid content was determined by UV-VIS spectrometry, phytosterols and carotenoids were also analysed using HPLC-DAD. Total phenolic content was measured using Folin-Ciocalteu reagent and antioxidant activity by ABTS assay. The measured properties were then compared with industrially produced comfrey ointment. In macerated fats the increase in acid and peroxide value was determined. Furthermore, an increase in the content of total phytosterols and total carotenoids was observed. Using HPLC-DAD the content of -sitosterol and stigmasterol was determined, but carotenoids were not detected. Of the tocopherols, only DL--tocopherol acetate was detected. During maceration, the content of total phenolic compound in fat increased, which caused a change in antioxidant activity.

Le développement de méthodes de synthèse asymétriques a largement été exploré au cours des vingt dernières années et en particulier par le biais de réactifs organométalliques. Bien que ces processus mènent à d’excellents résultats en terme d’énantiodiscrimination, l’objectif de cette thèse a été de développer de nouveaux outils de synthèse peu onéreux, respectueux des fonctions sensibles environantes et permettant l’accès aux composés attendus avec de bons rendements et excès énantiomériques. Dans cet optique, des triorganozincates de lithium chiraux ont été étudiés. Des méthodes d’alkylation et d’arylation 1,2 énantiosélectives d’aldéhydes, comportant comme partenaire chiral la (R)-N-(2-iso-butoxybenzyl)-1- phenyléthanamine, ont ainsi été développées et mises en application sur divers aldéhydes. Les alcools secondaires correspondants ont été obtenus avec de bons rendements (jusqu'à 83%) et d’excellents excès énantiomériques (jusqu'à 99%). Ces procédures ont ensuite été appliquées à la synthèse asymétrique de produits naturels et/ou bioactifs tels que la Spiromastilactone A, la (R)-Néobénodine et la (R)-Orphénadrine. Par ailleurs, la synthèse de nouveaux ligands de type amino-alcool a été développée dans le but ultime de désymétriser des substrats de type imines cycliques. / The development of new asymetric methodologies have been widely explored during the last twenty years and in particular through organometallic reagents. Although these processes lead to excellent results in terms of enantiodiscrimination, the goal of this thesis was to develop new tools: cheap, chemoselective and allowing the access to the desired compounds with high yields and enantiomeric excesses. In this context, chiral lithium triorganozincates have been studied. Enantioselective nucleophilic 1,2 alkylation and arylation of aldehydes reactions, including (R)-N-(2-iso-butoxybenzyl)-1-phenylethanamine as the chiral ligand, have been optimized toward various aldehydes. The expected secondary chiral alcohols have been obtained with good yields (up to 83%) and high enantiomeric excesses (up to 99%).These processes have been then applied to the asymmetric synthesis of naturals and/or bioactive compounds as Spiromastilactone A, (R)-Neobenodine and (R)-Orphenadrine. Finally, the access to new amino-alcohols have been developed with the ultimate goal to engage those species as the chiral partner when reacting chiral lithium zincates with imines.

MSc (Chemistry) / Department of Chemistry / Rauvolfia caffra Sond, a species of evergreen trees and shrubs in the dogbane family, (Apocynaceae), is used as a medicinal plant among traditional communities in many countries for the treatment of malaria, diabetes, coughs, gastrointestinal disturbances, skin infections, impotence, insomnia, diarrhoea, dysentery, scabies, worm infections, and both parasitic and microbial infections. Phytochemical studies have revealed that indole alkaloids are the major constituents of the stem bark. However, there are limited studies linking the compounds with the ethnomedicinal uses. The aim of this study is to isolate and characterize bioactive compounds from Rauvolfia caffra Sond. The highest phenolic content found in a fraction was 16.06±0.125 mg GAE/g, while the highest flavonoid content measured was 9.453±0.081 mg QE/g. In the DPPH free radical scavenging activity and reducing power tests, a lowest IC50 value of 0.022±0.003 μg/mL and IC0.5 value 0.518±0.044 μg/mL, respectively, was found. Six compounds were isolated from the stem bark, including lupeol, a pentacyclic tri-terpenoid isolated for the first time from the genus Rauvolfia; raucaffricine, a rare glycoalkaloid of the monoterpenoid indole class; N-methylsarpagine, an indole alkaloid isolated for the time from R. caffra and spegatrine, an indole alkaloid isolated for the first time from R. caffra, respectively. Concerning antimicrobial activity, the highest activity of a fraction was against B. cereus with MIC values as low as 12.5 mg/mL. One fraction at the tested concentration (250 μg/mL) decreased the viability of Plasmodium falciparum (4.149±6.979 %) with an IC50 value of 6.533 μg/mL. The crude extract and some fractions affected the viability of the Trypanosomes at the tested concentration (250 μg/mL), giving -0.133 ± 0.206 %, 11.334 ± 2.692 %, 1.026 ± 0.143 % and 20.769 ± 9.054 % with IC50 values of 18.50 μg/mL, 14.15 μg/mL, 15.58 μg/mL and 34.71 μg/mL, respectively. Furthermore, the fractions did not show significant cytotoxic effects at a concentration of 50 μg/mL. / NRF

M. Tech. (Department of Chemistry, Faculty of Applied and Computer Sciences), Vaal University of Technology / The present study includes the use of a green synthetic method to prepare copper and silver nanoparticles using chitosan, aqueous extracts of Camellia sinensis, Combretum molle and Melia azedarach linn leaves. This study aims to investigate the influence of capping and precursor concentration on the properties of silver nanoparticles with emphasis on the medicinal plants chosen. The effect of capping agent on the properties of copper nanoparticles is also investigated. The phytochemical properties of plant extracts and the antimicrobial activity of the synthesized particles were also studied; this was achieved by using microdilution bioassay. Decoction method was used to extract secondary metabolites from plant leaves. Preliminary phytochemical screening carried out on the aqueous extracts of the plant leaves showed the presence of tannins, proteins, flavonoids, phenols, and carbohydrates. The total phenolic and flavonoids content of the aqueous extract was determined using spectroscopic methods. The highest phenolic content was found in the aqueous extract of Combretum molle (135 mg/g), and the highest flavonoid content was found in the aqueous extract of Camellia sinensis (0.4 mg/g). Characterization was done by a combination of spectroscopic, microscopy and XRD techniques. Both the size and shape of the synthesized silver nanoparticles were dependent on the identity of the capping molecule, precursor and capping agent concentration as depicted from their TEM and XRD results. Silver nanoparticles were found to be predominantly spherical. The capping agent concentration was also found to influence the degree of agglomeration, with an increase in capping agent concentration giving lesser agglomeration. FTIR spectral analysis showed that silver nanoparticles interact with bioactive compounds found in the plants through the hydroxyl functional group. Other shapes including diamond were observed for the effect of precursor concentration. The XRD micrographs revealed a face-centered cubic geometry and the phase remained the same with an increase in precursor concentration. The synthesized silver nanoparticles were all blue shifted compared to the bulk material. The TEM results revealed that copper nanoparticles with different sizes and shapes were successfully synthesized. All the prepared copper and silver nanoparticles showed satisfactory antifungal and antibacterial activity against Candida albicans, Cryptococcus neoformans, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumonia and Pseudomonas aeruginosa. The capping molecules used in this study also showed some antibacterial and antifungal activity against the selected strains. However nanoparticles performed better than these capping molecules. Both silver and copper nanoparticles were found to be more active against gram-negative bacteria compared to gram-positive bacteria. Amongst all the prepared silver nanoparticles Combretum molle capped nanoparticles were found to be the most active nanoparticles. Also with copper nanoparticles, it was found that Combretum molle capped nanoparticles were the most active nanoparticles. Between the two metal nanoparticles, silver nanoparticles showed high antibacterial and antifungal activity compared to copper nanoparticles. The antioxidant activity of silver nanoparticles was assessed using 2.2-diphenyl-1-picrylhydrazyl. Silver nanoparticles were found to have some antioxidant activity. However, the capping molecules were found to be more active than the synthesized nanoparticles. This observation is attributed to the presence of some bioactive compounds in the plant extracts.

Tesis por compendio / [ES] El proceso de emulsificación de aceites ricos en compuestos bioactivos permite su mejor aplicación y conservación durante el tiempo de almacenamiento. Entre los diversos mecanismos de emulsificación, se destaca el método de Pickering ya que utiliza nanopartículas sólidas naturales en sustitución de los tensioactivos artificiales. Debido a sus propiedades antioxidantes, no toxicidad y disponibilidad, en este trabajo se estudiaron distintas modificaciones del quitosano para su potencial aplicación como partícula de Pickering. Las modificaciones estudiadas fueron la autoagregación, también denominada desprotonación, y el entrecruzamiento con tripolifosfato de sodio. Se evaluó el comportamiento de estas partículas emulsionando aceite de café tostado, un subproducto de la industria de café con un alto contenido de compuestos bioactivos y compuestos volátiles de interés. Posteriormente, se analizaron las propiedades físico-químicas y la estabilidad de las microcápsulas producidas tras el secado de las emulsiones mediante técnicas de secado por atomización y liofilización. Todas las emulsiones se caracterizaron por tener un comportamiento reológico pseudoplástico, sufriendo desintegración a lo largo del proceso de digestión. Las emulsiones formuladas con nanopartículas de quitosano desprotonadas y menor concentración de aceite mostraron una mejor estabilización y, en consecuencia, una mayor bioaccesibilidad de los compuestos fenólicos totales. Las diferentes nanopartículas de quitosano se caracterizaron estudiando su carga superficial, distribución del tamaño de partícula, microestructura y afinidad agua/aceite. A medida que se aumentó la concentración de estas partículas, se afectó positivamente la viscosidad de las emulsiones debido a la formación de una red tridimensional en la fase continua. Las nanopartículas obtenidas al entrecruzar quitosano con tripolifosfato de sodio fueron más pequeñas, dando como resultado emulsiones con gotas más pequeñas. Las emulsiones de Pickering que contenían un 10% de aceite de café tostado se secaron por atomización y se liofilizaron utilizando las diferentes nanopartículas de quitosano estudiadas y maltodextrina como agentes portadores. Las microcápsulas obtenidas tuvieron la humedad, actividad del agua y solubilidad adecuada para su manipulación y almacenamiento. La presencia de nanopartículas de quitosano permitió una mayor retención de aceite en las microcápsulas y mayor eficiencia de encapsulación. Los compuestos bioactivos y las propiedades antioxidantes se conservaron mejor durante la liofilización. Por otro lado, las microcápsulas obtenidas por atomización presentaron mayor protección de estos compuestos durante la digestión. Las microcápsulas formuladas con nanopartículas desprotonadas fueron sometidas a almacenamiento durante 30 días a 25 ºC. Durante el almacenamiento, se evaluó la protección contra la oxidación de lípidos y la liberación de volátiles. Las isotermas de sorción de agua de estas muestras se determinaron también previamente en las condiciones de almacenamiento. Ambas muestras presentaron isotermas del tipo II, lo que permitió un buen ajuste del modelo de GAB a los datos experimentales. La determinación del índice de peróxido y del contenido de dienos conjugados dio lugar a valores adecuados durante el almacenamiento, aunque las muestras liofilizadas presentaron una ligera tendencia a la oxidación debido a la mayor cantidad de aceite superficial. Aunque hubo ligeras diferencias entre las muestras secas, todas mostraron menos pérdida de aromas totales (~28%) en comparación con el aceite no encapsulado (~51%) al final del almacenamiento. Así, se concluyó que las nanopartículas de quitosano estudiadas fueron eficientes para encapsular el aceite de café tostado y preservar sus características frente a la acción de agentes externos. / [CA] El procés d'emulsificació d'olis rics en compostos bioactius permet la seua millor aplicació i conservació durant el temps d'emmagatzematge. Entre els diversos mecanismes d'emulsificació, destaca el mètode de Pickering, ja que utilitza nanopartícules sòlides naturals en substitució als tensioactius artificials. A causa de la seua propietat antioxidant, de la no toxicitat i de la disponibilitat, aquest treball va buscar analitzar el quitosà i les seues modificacions com potencials partícules de Pickering. Les modificacions estudiades van ser la autoagregació, també anomenada desprotonació, i l'entrecreuament amb tripolifosfat de sodi. Es va avaluar el comportament d'aquestes partícules emulsionant oli de cafè torrat, un subproducte de la indústria del cafè amb un alt contingut de compostos bioactius i volàtils d'interès. Posteriorment, es van analitzar les propietats fisicoquímiques i l'estabilitat de les microcàpsules produïdes després de l'assecat de les emulsions mitjançant tècniques d'assecatge per atomització i liofilització. Totes les emulsions tenien un comportament reològic pseudoplàstic, sofrint desintegració al llarg del procés de digestió. Les emulsions formulades amb nanopartícules de quitosà desprotonades i menor concentració d'oli van mostrar una millor estabilització i, en conseqüència, una major bioaccesibilitat als compostos fenòlics totals. Les diferents nanopartícules de quitosà es van caracteritzar estudiant la seua càrrega superficial, distribució del tamany de partícula, microestructura i afinitat aigua/oli. A mesura que es va augmentar la concentració d'aquestes partícules, es va afectar positivament la viscositat de les emulsions a causa de la formació d'una xarxa tridimensional en la fase contínua. Les nanopartícules obtingudes a l'entrecreuar quitosà amb tripolifosfat de sodi van ser més menudes, donant com a resultat emulsions amb gotes més menudes també. Les emulsions de Pickering que contenien un 10% d'oli de cafè torrat es van assecar per atomització i es liofilitzaren utilitzant les diferents nanopartícules de quitosà estudiades i maltodextrina com a agents portadors. Les microcàpsules obtingudes van obtenir una humitat, activitat de l'aigua i solubilitat adequada per a la seua manipulació i emmagatzematge. La presència de nanopartícules de quitosà va permetre major retenció d'oli en les microcàpsules i major eficiència d'encapsulació. Els compostos bioactius i les propietats antioxidants es van conservar millor durant la liofilització. D'altra banda, les microcàpsules obtingudes per atomització presentaren major protecció d'aquests compostos durant la digestió. Les microcàpsules formulades amb nanopartícules desprotonades també van ser sotmeses a la prova d'emmagatzematge durant 30 dies a 25°C. Durant l'emmagatzematge, es va avaluar la seua protecció contra l'oxidació de lípids i l'alliberament de volàtils. Per això, les isotermes de sorció d'aigua d'aquestes mostres es van determinar prèviament en les condicions d'emmagatzematge. Les dues mostres van presentar isotermes de tipus II, el que va permetre un bon ajust del model de GAB a les dades experimentals. L'índex de peròxids i el contingut de diens conjugats van resultar en valors adequats durant l'emmagatzematge, encara que les mostres liofilitzades van presentar una lleugera tendència a l'oxidació a causa de la major quantitat d'oli superficial. Encara que va haver lleugeres diferències entre les mostres seques, totes van mostrar menys pèrdua d'aromes totals (~28%) en comparació amb l'oli no encapsulat (~51%) a la fi de l'emmagatzematge. Així, es va concloure que les nanopartícules de quitosà estudiades van ser eficients per encapsular l'oli de cafè torrat i preservar les seues característiques enfront de l'acció d'agents externs. / [EN] The emulsification process of bioactive-rich oils makes possible their better application and preservation over the storage time. Among the many emulsification mechanisms, the Pickering method has been highlighted as it uses natural solid nanoparticles in replacement of artificial surfactants. Due to the antioxidant properties, non-toxicity and availability, this work aimed at studying chitosan modifications to produce potential Pickering particles. The studied modifications comprised self-aggregation, also called deprotonation, and crosslinking with sodium tripolyphosphate. The performance of these particles was evaluated in the emulsification of roasted coffee oil, a by-product of the coffee industry with a high content of bioactive and volatile compounds of interest. Subsequently, the physicochemical properties and stability of the microcapsules produced after drying the emulsions using spray-drying and lyophilization techniques were analyzed. All emulsions were characterized as shear-thinning, being them destabilized over the digestion process. Emulsions formulated with deprotonated chitosan nanoparticles and lower oil concentrations showed better stabilization and, consequently, greater bioaccessibility of total phenolic compounds. The different chitosan nanoparticles were characterized regarding surface charge, particle size distribution, microstructure and oil/water affinity. Deprotonated chitosan nanoparticles had a larger particle size, which resulted in emulsions with larger oil droplets. As the concentration of these particles increased, the viscosity of the emulsions was positively affected by the formation of a three-dimensional network in the continuous phase. The nanoparticles obtained by crosslinking with sodium tripolyphosphate were smaller, resulting in emulsions with smaller droplets. The viscosity of these emulsions was lower and little affected by the concentration of particles. Pickering emulsions containing 10% roasted coffee oil were spray-dried and freeze-dried, using the different studied chitosan nanoparticles and maltodextrin as carrier agents. The resulting microcapsules showed adequate moisture content, water activity and solubility for subsequent handling and storage. The presence of chitosan nanoparticles resulted in greater oil retention in the microcapsules and higher encapsulation efficiency. Microcapsules obtained by spray-drying had a more regular spherical shape, while the microparticles obtained by freeze-drying were larger with irregular morphology. Bioactive compounds and antioxidant properties were more preserved during freeze-drying. On the other hand, spray drying allowed greater protection of these compounds during the in vitro digestion. The spray- and freeze-dried microcapsules formulated with deprotonated nanoparticles were subjected to the storage test for 30 days at 25 ºC. During storage, their protection against lipid oxidation and volatile release were evaluated. The water sorption isotherms of these samples were previously determined under the storage conditions. Both samples presented type II isotherms, which resulted in a good fitting accuracy of the GAB model to the experimental data. The peroxide index and the conjugated dienes content resulted in adequate values during storage, although the freeze-dried samples showed a slightly higher tendency to oxidation due to the higher amount of surface oil. Although slight differences were observed between the dried samples, both of them showed less loss of total volatile compounds (~28%) when compared to the non-encapsulated oil (~51%) at the end of storage. Thus, it was concluded that the studied chitosan nanoparticles were efficient to encapsulate roasted coffee oil and to preserve its characteristics against the action of external agents. / The authors would like to thank the project RTI-2018-099738-B-C22 from the ‘Ministerio de Ciencia, Innovación y Universidades’, the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES) - (Finance Code 001; Grant number 88887.468140/2019-00) and the São Paulo Research Foundation (FAPESP – Grant number 2016/22727-8) for the financial support. / Franco Ribeiro, E. (2021). Microencapsulation of roasted coffee oil from chitosan nanoparticles-stabilized Pickering emulsions [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/163234 / Compendio

HIV-1 protease inhibitor drugs are important components of current antiretroviral therapy (cART). The cART treatment regimens dramatically improved life expectancy and mortality of patients with HIV-1 infection and AIDS. However, new and improved protease inhibitor drugs are essential for future treatment options. To this end, syntheses of optically active (3a<i>S</i>,4<i>S</i>,7a<i>R</i>)-hexahydro-4<i>H</i>-furo[2,3-<i>b</i>]pyran-4-ol, (3a<i>R</i>,4<i>R</i>,7a<i>S</i>)-hexahydro-4<i>H</i>-furo[2,3-b]pyran-4-ol, and (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-hexahydrofuro[2,3-6]furan-3-ol have been accomplished. These stereochemically defined heterocyclic derivatives are important high-affinity P2 ligands for a variety of highly potent HIV-1 protease inhibitors. The key steps for the synthesis hexehydrofuropyranol involve an efficient Paternò-Büchi [2+2] photocycloaddition, catalytic hydrogenation, acid-catalyzed cyclization to form the racemic ligand alcohol, and enzymatic resolution with immobilized Amano Lipase PS-30. Optically active ligand alcohols were obtained with high enantiomeric purity. Enantiomer (-)-ligand alcohol has been converted to potent HIV-1 protease inhibitors. <div><br></div><div>(3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-Hexahydrofuro[2,3-<i>b</i>]furan-3-ol(<i>bis</i>-tetrahydrofuran) is a key subunit of darunavir, an FDA approved HIV-1 protease inhibitor drug which is widely used for the treatment of HIV/AIDS patients. This stereochemically defined bicyclic heterocycle is also embedded in a variety of highly potent HIV-1 protease inhibitors. The synthesis of optically active <i>bis</i>-tetrahydrofuran was achieved in optically pure form utilizing commercially available and inexpensive 1,2-<i>O</i>-isopropylidene-α-D-xylofuranose or 1,2-O-isopropylidene-α-D-glucofuranose as the starting material. The key steps involve a highly stereoselective substrate-controlled hydrogenation of ethyl 2-(dihydrofuran-3(2H)-ylidene)acetate, a Lewis acid-catalyzed anomeric reduction of a 1,2-<i>O</i>-isopropylidene-protected glycofuranoside, and a Baeyer-Villiger oxidation of a tetrahydrofuranyl-2-aldehyde derivative. Optically active (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-hexahydrofuro[2,3-<i>b</i>]furan-3-ol ligand was converted to darunavir efficiently. Furthermore, both furopyranol and bis-tetrahydrofuran ligand alcohols have been converted into a variety of potent HIV-1 protease inhibitors including inhibitors containing P2'-boronic acid ligands.<br></div><div><br></div><div>Diabetes mellitus is a chronic, progressive metabolic disorder that seriously threatens human health worldwide, particularly in developing countries. The prevalence of diabetes has been increasing steadily, especially in developing countries. Carambolaflavone A is a natural flavonoid isolated from the leaves of starfruit tree, <i>Averrhoacarambola</i>, in 2005. Carambolaflavone A possesses a <i>C</i>-aryl glycosidic linkage. Carambolaflavone A exhibited significant antihyperglycemic properties. More detailed biological studies reveal that it can lower acute blood glucose. The biology and chemistry of carambolaflavone A attracted our interest in synthesis and further design of interesting structural variants. A convergent total synthesis of carambolaflavone A has been accomplished. The synthesis highlights a bismuth triflate-catalyzed stereoselective C-aryl glycosylation of flavan and an appropriately protected D-fucose derivative as the key step. The glycosylation partners were synthesized from commercially available (±)-naringenin and D-(+)-galactose, respectively. An oxidative bromination and elimination reaction sequence was utilized to construct the flavone. The natural product is obtained in 10 steps (longest linear sequence) from D-(+)-galactose.<br></div>

Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2018-03-07T15:22:05Z No. of bitstreams: 1 2017 - Gabriela Vieira do Amaral.pdf: 1320069 bytes, checksum: bc0ab4f1fe7a912edee70092297020a1 (MD5) / Made available in DSpace on 2018-03-07T15:22:12Z (GMT). No. of bitstreams: 1 2017 - Gabriela Vieira do Amaral.pdf: 1320069 bytes, checksum: bc0ab4f1fe7a912edee70092297020a1 (MD5) Previous issue date: 2017-07-17 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Emerging supercritical carbon dioxide (SCCD) technology has been studied as a cold pasteurizing agent, however, few studies are available on its efficiency in dairy products. In this study, the effects of SCCD processing by different pressures 14, 16 and 18 MPa (35 ? 2 ?C / 10 min) on whey drink, whey drink and grape juice were investigated in comparison To conventional pasteurization (heat treatment at 72 ?C / 15 s). Physicochemical analyzes of pH, titratable acidity, total soluble solids, phenolic compounds, anthocyanins, antioxidant activity, angiotensin converting enzyme (ACE) inhibitory activity and volatile compounds were performed. The color, particle size, rheology, physical stability, as well as microbiological quality and sensory analysis of beverages were also smoothed. The results of this study evidenced the absence of differences between treatments in pH, titratable acidity, soluble solids, total anthocyanins and DPPH activity (p> 0.05). A direct relationship between SCCD pressure and ACE inhibitory activity was observed, with 34.63, 38.75 and 44.31% (14, 16 and 18 MPa, respectively). Few differences were found in the volatile compounds profile. The beverage processing by SCCD resulted in a product with lower particle diameter, lower consistency index and a reduction in pseudoplastic character compared to the beverage treated by the conventional process. No effect of high pressure CO2 on the sensorial attributes of the drink was observed for the studied levels. Consumers found no difference between CO2 treated beverages and heat-treated beverages. The results confirm the processing of SCCD as a promising technology for the non-thermal treatment of grape whey drink made available a health and wellness promoter beverage. Background: Non-thermal food processing is configured as an interesting alternative for the food industry due to the increased nutrient retention and minimal sensory changes in processed products. Scope and approach: The aim of this review is to address the potential of supercritical carbon dioxide technology, emphasizing milk and dairy processing, including the historical aspects, main advantages, microbial inactivation mechanisms, as well as effects in some quality parameters of dairy products. Key findings and conclusions: The use of supercritical carbon dioxide technology (SC-CO2) presents great potential application in dairy processing, since it is effective to reduce microbial load when compared to the pasteurization process, thus obtaining a product with greater shelf life and better organoleptic properties with minimal and sometimes positive changes in the intrinsic quality parameters The effect of supercritical carbon dioxide technology (SCCD, 140, 160, and 180 bar at 35 ? 2 ?C for 10 min) on whey-grape juice drink characteristics was investigated. Physicochemical characterization (pH, titratable acidity, total soluble solids), bioactive compounds ( phenolic compunds, anthocyanins , DPPH and ACE activity) and the volatile compounds were performed. Absence of differences were found among treatments for pH, titratable acidity, soluble solids, total anthocyanins and DPPH activity (p>0.05). A direct relationship between SCCD pressure and ACE inhibitory activity was observed, with 34.63, 38.75, and 44.31% (140, 160, and 180 bar, respectively). Regards the volatile compounds, it was noted few differences except by the presence of ketones. The findings confirm the SCCD processing as a potential promising technology to the conventional thermal treatment. The use of supercritical technology as a non-thermal pasteurization process of the whey-grape juice drink was investigated in this study. The effects of supercritical carbon dioxide at 14, 16, and 18 MPa (35 ? 2?C/10 min) on the physical and sensory properties of the beverage, when compared to conventional pasteurization (heat treatment at 72?C/15 s) were evaluated. High-pressure CO2 processing of whey-grape juice drink resulted in a product with lower particle diameter, lower consistency index, and a reduction in pseudoplastic character when compared to the beverage treated by the conventional process. No effect of high-pressure CO2 was observed on the sensory attributes of the beverage for the levels studied. Consumers did not find differences between the CO2-treated and heat-treated beverages. Our findings suggest the use of supercritical technology with carbon dioxide as an effective alternative for the production and availability of a health and wellness promoting beverage / A tecnologia emergente de di?xido de carbono supercr?tico (DCSC) vem sendo estudada como agente pasteuriza??o a frio, no entanto, s?o poucos os estudos dispon?veis a cerca da sua efici?ncia em derivados l?cteos. Neste estudo, foram investigados os efeitos do processamento do DCSC por diferentes press?es 14, 16 e 18 MPa (35 ? 2 ?C / 10 min) no whey drink de uva, bebida a base de soro de leite e suco de uva, em compara??o ? pasteuriza??o convencional (tratamento t?rmico a 72 ?C / 15 s). Foram realizadas an?lises f?sico-quimicas de pH, acidez titul?vel, s?lidos sol?veis totais, compostos fen?licos, antocianinas, atividade antioxidante, atividade inibidora da enzima conversora de angiotensina (ECA) e compostos vol?teis. Tamb?m foramam alisados a cor, o tamanho de part?cula, reologia, estabilidade f?sica, assim como a qualidade microbiol?gica e analise sensorial das bebidas. Os resultados deste estudo evidenciaram a aus?ncia de diferen?as entre os tratamentos nas an?lises de pH, acidez titul?vel, s?lidos sol?veis, antocianinas totais e atividade de DPPH (p> 0,05). Foi observada uma rela??o direta entre press?o DCSC e atividade inibit?ria ACE, com 34,63, 38,75 e 44,31% (14, 16 e 18 MPa, respectivamente). Poucas diferen?as foram encontratdas no perfil dos compostos vol?teis. O processamento das bebidas por DCSC resultou em um produto com menor di?metro de part?cula, menor ?ndice de consist?ncia e uma redu??o no car?ter pseudopl?stico em compara??o com a bebida tratada pelo processo convencional. N?o foi observado efeito de CO2 de alta press?o nos atributos sensoriais da bebida para os n?veis estudados. Os consumidores n?o encontraram diferen?as entre as bebidas tratadas com CO2 e as bebidas tratadas termicamente. Os resultados confirmam o processamento do DCSC como uma tecnologia promissora para o tratamento n?o t?rmico de whey drink de uva disponibilizado uma bebida promotora de sa?de e bem-estar Antecedentes: Os processamentos de alimentos n?o t?rmicos s?o configurados como uma alternativa interessante para a ind?stria de alimentos devido ao aumento da reten??o de nutrientes e mudan?as sensoriais m?nimas nos produtos processados. ?mbito e abordagem: o objetivo desta revis?o ? abordar o potencial da tecnologia de di?xido de carbono supercr?tico, enfatizando o processamento de leite e l?cteos, incluindo os aspectos hist?ricos, as principais vantagens, os mecanismos de inativa??o microbiana, bem como os efeitos em alguns par?metros de qualidade dos produtos l?cteos. Principais conclus?es e conclus?es: o uso de tecnologia supercr?tica de di?xido de carbono (SC-CO2) apresenta grande potencial de aplica??o no processamento de l?cteos, uma vez que ? efetivo reduzir a carga microbiana quando comparado ao processo de pasteuriza??o, obtendo-se assim um produto com maior prateleira e melhores propriedades sensoriais com mudan?as m?nimas e ?s vezes positivas nos par?metros de qualidade intr?nseca. O efeito da tecnologia de di?xido de carbono supercr?tico (SCCD, 140, 160 e 180 bar a 35 ? 2 ?C durante 10 min) em caracter?sticas de bebidas de suco de uva foi investigado. Caracteriza??o f?sico-qu?mica (pH, acidez titul?vel, s?lidos sol?veis totais), compostos bioativos (compostos fen?licos, antocianinas, DPPH e atividade ACE) e os compostos vol?teis foram realizados. A aus?ncia de diferen?as foi encontrada entre tratamentos para pH, acidez titul?vel, s?lidos sol?veis, antocianinas totais e atividade de DPPH (p> 0,05). Foi observada uma rela??o direta entre press?o SCCD e atividade inibit?ria ACE, com 34,63, 38,75 e 44,31% (140, 160 e 180 bar, respectivamente). Atende aos compostos vol?teis, observou-se poucas diferen?as, exceto pela presen?a de cetonas. Os resultados confirmam o processamento do SCCD como uma potencial tecnologia promissora para o tratamento t?rmico convencional O uso da tecnologia supercr?tica como processo de pasteuriza??o a frio da bebida de suco de uva e soro de uva foi investigado neste estudo. Os efeitos do di?xido de carbono supercr?tico em 14, 16 e 18 MPa (35 ? 2 ?C / 10 min) nas propriedades f?sicas e sensoriais da bebida, quando comparados ? pasteuriza??o convencional (tratamento t?rmico a 72 ?C / 15 s) Foram avaliados. O processamento de CO2 de alta press?o da bebida de suco de soro de soro de leite resultou em um produto com menor di?metro de part?cula, menor ?ndice de consist?ncia e uma redu??o no car?ter pseudopl?stico em compara??o com a bebida tratada pelo processo convencional. N?o foi observado efeito de CO2 de alta press?o nos atributos sensoriais da bebida para os n?veis estudados. Os consumidores n?o encontraram diferen?as entre as bebidas tratadas com CO2 e as bebidas tratadas termicamente. Nossas descobertas sugerem o uso da tecnologia supercr?tica com di?xido de carbono como uma alternativa efetiva para a produ??o e disponibilidade de uma bebida promotora de sa?de e bem-estar

Els brassinoesteroides són fitohormones naturals que presenten un potencial molt prometedor per a ser aplicats a l’agricultura. L’elevat cost d’obtenció d’aquests compostos ha estimulat la recerca d’anàlegs que ofereixin una bona relació entre la seva activitat biològica i el seu cost. En aquest sentit, es creu interessant abordar la cerca de compostos d’estructura no esteroïdal amb activitat brassinosteroide mitjançant mètodes computacionals. Per assolir aquest objectiu s’han plantejat dos enfocaments: per una banda, buscar estructures totalment noves i, per l’altra, buscar estructures que puguin mimetitzar només l’esquelet esteroidal d’anàlegs brassinoesteroides androstànics actius per a, posteriorment, ancorar hi la cadena addient. Amb la primera aproximació s’han realitzat processos de virtual screening sobre bases de dades de screening compounds comercials mitjançant dues estratègies: un model de QSAR, desenvolupat amb descriptors independents de l’alineament amb el programa ALMOND, i l’aplicació de la metodologia FLAP. Després d’un procés de filtració, a partir dels dos mètodes s’han proposat una serie de candidats, l’activitat dels quals ha estat avaluada amb el test d’inclinació de la làmina d’arròs (RLIT). En total, s’han trobat 7 hits, 4 dels quals formen una sèrie en la que comparteixen l’estructura de N (2 hidroxietil)piperazina. Aquests compostos es plantegen com a nous referents per obtenir estructures no esteroidals amb activitat brassinoesteroide. Per altra banda, amb la segona aproximació, s’ha aplicat la metodologia de scaffold hopping amb el programa SHOP per trobar estructures que puguin mimetitzar esquelets androstànics brassinoesteroides. Aquesta metodologia s’ha aplicat sobre dues bases de dades: una de building blocks comercials i una disenyada ad hoc prenent com a referència estructures basades en coneixements previs. Després d’una etapa de selecció mitjançant alineaments flexibles efectuats amb el programa MOE, 11 estructures han estat proposades per a la síntesis d’anàlegs. S’ha intentat la síntesis de 3 compostos a partir d’estructures anàlogues de l’esquelet androstànic escollides preliminarment. Els grups protectors escollits i les condicions de reacció assajades no han rendit els compostos desitjats però han proporcionat informació per afrontar la síntesi de futurs anàlegs brassinoesteroides amb estructures no esteroïdals. / Los brasinoesteroides son fitohormonas naturales que presentan un potencial muy prometedor para ser aplicados en la agricultura. El elevado coste de obtención de estos compuestos ha estimulado la búsqueda de análogos que ofrezcan una buena relación entre su actividad y su coste. En este sentido, se cree interesante abordar la búsqueda de compuestos de estructura no esteroidal con actividad brasinoesteroide mediante técnicas computacionales. Para lograr este objetivo se han planteado dos enfoques: por un lado, buscar estructuras totalmente nuevas y, por el otro, buscar estructuras que puedan mimetizar solo el esqueleto esteroidal de análogos brasinoesteroides androstánicos activos para, posteriormente, anclar la cadena adecuada. Con la primera aproximación se han realizado procesos de virtual screening sobre bases de datos de screening compounds comerciales mediante dos estrategias: un modelo de QSAR, desarrollado con descriptores independientes del alineamiento con el programa ALMOND, y la aplicación de la metodología FLAP. Después de un proceso de filtrado, a partir de los dos métodos se han propuesto una serie de candidatos, la actividad de los cuales ha sido evaluada con el test de inclinación de la lámina de arroz (RLIT). En total, se han encontrado 7 hits, 4 de los cuales forman una serie que comparte la estructura de N (2 hidroxietil)piperazina. Estos compuestos se plantean como nuevos referentes para obtener estructuras no esteroidales con actividad brasinoesteroide. Por otro lado, con la segunda aproximación, se ha aplicado la metodología de scaffold hopping con el programa SHOP para encontrar estructuras que puedan mimetizar esqueletos androstánicos brasinoesteroides. Esta metodología se ha aplicado sobre dos bases de datos: una de building blocks comerciales y otra diseñada ad hoc tomando como referencia estructuras basadas en conocimientos previos. Después de una etapa de selección mediante alineamientos flexibles realizada con el programa MOE, 11 estructuras han sido propuestas para la síntesis de análogos. Se ha intentado la síntesis de 3 nuevos compuestos a partir de estructuras análogas del esqueleto androstánico escogidas preliminarmente. Los grupos protectores escogidos i las condiciones de reacción ensayadas no han rendido los compuestos deseados pero han proporcionado información para afrontar la síntesis de futuros análogos brasinoesteroides con estructuras no esteroidales. / Brassinosteroids are natural phytohormones that present a promising potential in agricultural applications. The high cost to obtain these compounds has promoted the research of analogues that offer a good relationship between their biological activity and their cost. Keeping this idea in mind, the search of compounds with non-steroidal structure with brassinosteroid activity using computational methods was considered an interesting goal. To achieve this objective two approaches has been proposed: on one side, to search completely new structures and, on the other, to search structures mimetic to the steroidal skeleton of active androstane brassinosteroid analogues, where the adequate side chain has to be anchored. With the first approach, virtual screening processes over commercial screening compound databases have been performed using two strategies: a QSAR model developed with alignment-free descriptors with the program ALMOND, and the application of FLAP methodology. After a filtering process, some structures have been proposed as candidates, whose biological activity in the Rice Lamina Inclination Test (RLIT) has been measured. Totally, 7 hits have been found, from which 4 form a series sharing the N (2 hidroxiethyl)piperazine. These compounds are proposed as new referents to find non steroidal structures with brassinosteroid activity. With the second approach, the scaffold hopping methodology has been applied with SHOP program to find structures mimetic to androstane brassinosteroid skeletons. This methodology has been applied over two databases: a commercial building blocks one and an ad hoc designed one, taking as reference structures based on previous knowledge. After a filtering step with flexible alignments performed with the program MOE, 11 structures have been proposed for the synthesis of new compounds. The synthesis of 3 new compounds has been tried starting from preliminary selected structures analogous to the androstane skeleton. The chosen protecting groups and the tested reaction conditions have not yielded the desired compounds but have given information to face the future synthesis of brassinosteroid analogues with non-steroidal structures.

<p>U okviru ove doktorske disertacije ispitane su i<br />poređene različite ekstrakcione tehnike korena<br />gaveza, lista crnog duda i peteljki tre&scaron;nje. Poređene<br />su konvencionalne i savremene ekstrakcione<br />tehnike i izvedena je optimizacija ekstrakcionih<br />postupaka s ciljem dobijanja ekstrakata ispitivanih<br />biljnih vrsta sa najvećom bioaktivno&scaron;ću. Za svaku<br />ekstrakcionu tehniku ispitan je uticaj najznačajnijih<br />parametara: maceracija (rastvarač i vreme<br />ekstrakcije), ubrzana ekstrakcija (temperatura i<br />rastvarač), supekritična ekstrakcija (pritisak i<br />koncentracija ko-rastvarača) i ekstrakcija<br />subkritičnom vodom (temperatura, pritisak, vreme<br />ekstrakcije i brzina me&scaron;anja). Ekstrakcija polifenola<br />korena gaveza, lista crnog duda i peteljki tre&scaron;nje je<br />bila najefikasnija ekstrakcijom subkritičnom<br />vodom. Primenjene su tehnika visokopritisne tečne<br />hromatografije spregnute sa masenom<br />spektrometrijom uz primenu različitih masenih<br />analizatora, masenog analizatora na bazi vremena<br />preleta jona i tandema kvadrupolnog i analizatora<br />na bazi vremena preleta jona. Za karakterizaciju<br />dobijenih ekstrakata instrumentalnom analizom su<br />određene kvalitativne i kvantitativne karakteristike dobijenih ekstrakata korena gaveza, lista crnog duda i peteljki tre&scaron;nje. HPLC-ESI-QTOF-MS/MS analizom ekstrakata identifikovano je vi&scaron;e od 27 novih jedinjenja različitih hemijskih klasa u svakom od ispitivanih biljnih matriksa.</p> / <p>Within the scope of this doctoral dissertation,<br />different extraction techniques of comfrey root,<br />black mulberry leaves and sweet cherry stems were<br />applied and compared. Conventional and novel<br />extraction techniques were optimized and<br />compared in order to obtain plant extracts with the<br />highest content of bioactive compounds. The<br />influence of the most important parameters was<br />investigated for each extraction technique:<br />maceration (solvent and extraction time),<br />accelerated solvent extraction (temperature and<br />solvent), supercritical fluid extraction (co-solvent<br />percentage and pressure) and subcritical water<br />extraction (temperature, pressure, extraction time<br />and agitation rate). Extraction of polyphenolic<br />compounds from comfrey root, black mulberry<br />leaves and sweet cherry stems was the most<br />effective using subcritical water. High-pressure<br />liquid chromatography coupled to mass<br />spectrometry techniques using time-of-flight and<br />quadrupole-time-of-flight mass analyzers have<br />been used to characterize bioactive compounds.<br />Qualitative and quantitative characteristics of the<br />obtained comfrey root, black mulberry leaves and sweet cherry stem extracts were determined. HPLC-ESI-QTOF-MS/MS revealed the presence of more than 27 compounds of different chemical classes that have been identified for the first time in&nbsp; the plant matrix.</p>

<p>  </p> <p>Organic synthesis is the application of one or more reactions to the preparation of a particular target molecule, and can pertain to a single-step transformation or to a number of sequential chemical steps depicted by a scheme overall. The selection of a reaction or series of reactions while considering chemo-, regio-, and stereoselectivities in addition to protecting group strategies & redox manipulations highlights the complexity in designing & executing a synthetic plan while making a judgement about what is the most effective and efficient plan to synthesize any given chemical compound among numerous available options. To this end, chemical synthesis is the unifying theme of this thesis & was utilized and strategically applied to construct increasingly complex and diverse molecular architectures. </p> <p>Being the precise science that organic chemistry is, this discipline extends into many areas such as technology, biology & medicine, and even into the fine arts since it fosters unparalleled creativity and imagination in its practice. Research foci in chemical synthesis can encompass both the discovery and development of powerful reactions and the invention of strategies for the construction of defined target molecules, natural or man-made, more or less complex. Studies in the former area, synthetic methodology, fuel and enable studies in the latter area, target molecule and total synthesis campaigns, where the latter area offers a testing ground for the former. Consequently, the bulk of this research work is in organic methodology and will be covered in greater depth during chapters 2 and 3 where strategies, optimizations, & analyses are elaborated upon in light of searching & navigating the vast body of chemical literature in an effort to broaden and strengthen one's laboratory expertise as a synthetic chemist. Lastly, chapter 4 focuses not on traditional synthesis but on organic structure analysis relying on various techniques such as nuclear magnetic resonance (NMR), infrared (IR), ultraviolet-visible (UV-Vis) spectroscopy in combination with mass spectrometry (MS) and/or X-ray crystallography to hypothesize and confirm established structures, specifically phenolic oligomers. An ability to use spectroscopic data to evaluate organic structures by combining practical experience with fundamental knowledge will serve as a hallmark skill in one’s ability to problem-solve as an organic chemist.</p>