Flavonoids are naturally occurring compounds that are consumed regularly in the diet. The property of flavonoids, which they are most commonly known for, is their antioxidant activity. Other potential pharmaceutical applications of flavonoids can be related to their enzyme inhibition, anti-allergic, anti-inflammatory, anti-microbial and anti-cancer properties. Lipases have been used effectively in the production of flavonoid ester derivatives that have shown both increased antioxidant and antimicrobial activity. Enzymatic esterifications of flavonoids are performed in organic solvents that increase substrate solubility of complex organic molecules. For the esterification of compounds in non-aqueous reaction conditions, vinyl esters are often preferred as substrates compared to carboxylic acids (which can be involved in reversible reactions, due to the formation of the by-product, water). In this study a group of vinyl esters of tert-butoxycarbonylated amino acid derivatives were synthesized to study alongside a range of commercially available vinyl esters. The synthesis of ester derivatives of naringin using a range of hydrolytic enzymes has been studied. A range of small to medium sized commercially available vinyl esters (C2- C10), as well as amino acid vinyl esters were selected for the biotransformations. For the esterification of naringin, small-scale reactions were carried out for 72 hrs and the reaction mixtures were analysed by HPLC. Lipases from the species Pseudomonas stutzeri, Candida antarctica and Alcaligenes spp. performed more than 80% conversion of naringin with some of the selected acylating agents. Reactions carried out with P. stutzeri lipase were scaled up to isolate the product of the biotransformation. None of the screened enzymes were successful in the acylation of naringin with the amino acid vinyl esters. Assays were carried out to compare the antioxidant activity of naringin and the synthesized derivatives. Two of the acyl derivatives showed a greater antioxidant activity in the reduction of Cu2+, compared to naringin. Aminoglycosides are antibiotics that have anti-bacterial properties. As well as their anti-bacterial properties some have been employed for their ability to suppress stop codons, which is a useful property in reducing symptoms of some hereditary disorders. In the present work attempts were made to derivatise an aminoglycoside by acylating it with the amino acid vinyl esters, using hydrolytic enzymes. Despite screening with various proteases in different solvents, the acylation of amikacin was not succesful during this investigation.

Tertiary alcohols are a common functional group in many natural products, pharmaceuticals and agrochemicals. The ability to produce highly enantiomerically pure tertiary alcohols is therefore an important goal in synthetic chemistry. The synthesis of chiral tertiary alcohol precursors has been achieved via enzymatic desymmetrisation with the lipase Amano L, AK to generate (S)-(2-(hydroxymethyl)oxiran-2-yl)methyl acetate in 42% isolated yield and 97% enantiomeric excess. The reaction was also attempted with an immobilised lipase from R. miehei yielding the product in 82-90% yield and up to 89% ee. The enantioselective ring-opening of the epoxide using different amines has been developed in high yields generating enantiomerically pure β-amino tertiary alcohol products. However, an undesired intramolecular migration of the acetyl group was observed during the epoxide opening with aliphatic primary amines resulting in prochiral triol products. To avoid such an intramolecular migration a TBS-protected derivative has been used to prepare the tertiary alcohol products with primary amines in good yields (43%-83%), without any loss of enantiomeric excess of the formed 'pseudo'-enantiomer .(S)-(2-(hydroxymethyl)oxiran-2-yl)methyl acetate has the potential to generate a large diversity of compounds; this reagent was also used as the starting material to generate azetidines in high yields.

No description available.

No description available.

Le cycle biogéochimique des lipides a été étudié en milieu marin côtier anthropisé. Ce travail est basé sur l’analyse chimique des stocks de lipides par CCM/DIF et la mesure de leur hydrolyse par les communautés bactériennes associées à ces stocks. Un développement méthodologique a eu pour objectif d’identifier les bactéries marines possédant l’activité lipase. Le substrat testé (ELF-palmitate), vendu comme marqueur potentiel des lipases, n’est pas hydrolysé spécifiquement par ces dernières. Par conséquent, il ne constitue pas un outil adéquat pour l’identification des bactéries lipases en milieu marin. L’étude temporelle réalisée en baie de Marseille a permis de déterminer les caractéristiques côtières propres à la baie, et de les comparer à des mesures obtenues antérieurement en milieu hauturier (site DYFAMED, Mer Ligure). Alors qu’ils représentent 1 à 7 % du carbone organique dissous (COD) en milieu hauturier, les lipides peuvent représenter jusqu’à 16% du COD en baie de Marseille en période de forte productivité, soulignant une forte accumulation de ces composés dans la matière organique dissoute (MOD). L’influence des apports côtiers dans la distribution des lipides biogéniques n’apparaît pas de manière aussi flagrante qu’on pouvait s’y attendre. Leur distribution est clairement contrôlée par les alternances saisonnières, comme dans le milieu hauturier. Ainsi, leur temps de résidence varie de 0.8-8 jours en fonction de l’activité bactérienne et de la saison. Les apports lipidiques d’origine anthropique (hydrocarbures) sont détectés à des concentrations parfois très élevées en 2007 en baie de Marseille. Entre 2007 et 2008, une forte diminution des concentrations en lipides et hydrocarbures dissous pourrait être liée à la mise en place d’un étage biologique dans le traitement des eaux usées de la ville de Marseille. Ce traitement supplémentaire aurait en effet pour principale conséquence de diminuer les apports en MOD dans les eaux usées rejetées par l’émissaire de Cortiou. Cette hypothèse implique que l’influence du panache de Cortiou soit visible jusqu’à la station Sofcom, située au milieu de la rade sud de la baie de Marseille / The biogeochemical cycle of lipids has been studied in a marine coastal anthropized environment. This work is based on chemical analysis of lipids by TLC/FID and the measurement of their hydrolysis rates by the associated bacterial communities. A methodological development aimed to identify lipase marine bacteria. The tested substrate (ELF-palmitate), sold as a potential marker of lipases, was not specifically hydrolyzed by the latter. Therefore, it is not an appropriate tool for the identification of marine lipase bacteria. The time series conducted in the Bay of Marseille (April 2007 – December 2008) allowed the determination of coastal characteristics of the bay and their comparison with previous measurements, obtained in the open Mediterranean Sea (DYFAMED, Ligurian sea). While they represent 1 to 7% of de dissolved organic carbon (DOC) at the offshore station, lipids may represent up to 16% of DOC in the Bay of Marseille, during periods of high productivity, underlining a strong accumulation of these compounds in the dissolved organic matter (DOM). The coastal inputs did not influence the distribution of biogenic lipids as was expected. Their distribution was clearly controlled by season, as in the offshore site. Accordingly, their residence time ranged from 0.8-8 days depending on bacterial enzyme activity and season. Lipidic anthropogenic inputs (hydrocarbons) were occasionally detected at very high concentrations in the Bay of Marseille during the year 2007. Between 2007 and 2008, a significant decrease in dissolved biogenic lipid and hydrocarbon concentrations could be related to the establishment of a biological treatment of wastewaters from Marseille. Indeed, this additional processing was expected to lead to the decrease of DOM inputs in wastewaters. This hypothesis implies that the plume of the wastewaters from Cortiou could influence the quality of OM at the Sofcom station, located in the centre of the Bay of Marseille.

Thèse de doctorat : Procédés biotechnologiques et alimentaires : INPL : 2006. / Titre provenant de l'écran-titre. Bibliogr.

Reproduction de : Thèse de doctorat : Biophysiologie des organismes et des populations : Le Mans : 2008. / Titre provenant de l'écran-titre. Bibliogr. p. 221-235.

Orientador: Luciana Francisco Fleuri / Resumo: Os resíduos agroindustriais são o destaque deste trabalho. Resíduos de laranja, uma cultura de extrema importância no Brasil, foram utilizados devido ao seu descarte abundante e pelo potencial em conter diversas moléculas de interesse biotecnológico. O objetivo foi avaliar os descartes do processamento de suco de laranja das principais variedades comerciais Hamlin, Pêra, Valência e Natal quanto à presença de enzimas e compostos bioativos. As lipases se mostraram presentes em todas as variedades de laranjas estudadas. Nas variedades Hamlin, Valência e Natal é a primeira vez que lipases são documentadas. As lipases do bagaço e polpa de Hamlin apresentaram 27,45 U/g e 31,13 U/g de atividade lipolítica, respectivamente. As proteases não foram encontradas a partir dos métodos utilizados, deixando em aberto a possibilidade de testar novas metodologias, como critério de caracterização e contribuição literária. O perfil químico dos compostos fenólicos existentes nos resíduos de laranja foi determinado e apresentou cerca de 80% de flavanonas no geral. Além disso, foi detectado alto teor de hesperidina (em mg/100 g) nos resíduos da variedade Pêra (3294,6); Hamlin (2903,2); Natal (2885,9) e Valência (2880,2). Atividades biológicas como antioxidante, antimicrobiana e sobre a viabilidade celular também foram abordadas, sendo que os resíduos apresentaram capacidade de redução do radical DPPH em torno de 70%. No entanto, não apresentaram potencial antimicrobiano frente às bactérias e fungos... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

FONSECA, Thiago de Sousa. Sínteses quimioenzimáticas dos fármacos (R)-luliconazol, (R)-clorprenalina e análogos e síntese química de substâncias imidazólicas. 2017. 210 f. Tese (Doutorado em Química)-Universidade Federal do Ceará, Fortaleza, 2017. / Submitted by José Orlando Soares de Oliveira (orlando.soares@bol.com.br) on 2017-08-24T13:18:12Z No. of bitstreams: 1 2017_dis_tsfonseca.pdf: 6070980 bytes, checksum: 5c887eadfe845e797a622899c103c8ae (MD5) / Rejected by Weslayne Nunes de Sales (weslaynesales@ufc.br), reason: O trabalho precisa ser normalização. Devolver o trabalho para o aluno para que ele realize as correções. Para acesso ao guia: http://www.biblioteca.ufc.br/publicacoes/41-guia-de-normalizacao Para acesso aos templates: http://www.biblioteca.ufc.br/educacao-de-usuarios/1234-templates Retirar a numeração dos elementos pré-textuais. Eles são contados, mas não são numerados. Refazer a folha de aprovação, conforme modelo estabelecido no Guia de Normalização da UFC e template. Inserir palavras-chave no resumo e no abstract. Listas de figuras, tabelas, esquemas, gráficos, abreviaturas e sumário devem ser digitados com espaçamento 1,5 entrelinhas Retirar as folhas que contém indicação de capítulo e título. Todo o texto deve ser digitado na cor preta, exceto as ilustrações. on 2017-08-24T13:54:08Z (GMT) / Submitted by José Orlando Soares de Oliveira (orlando.soares@bol.com.br) on 2017-08-25T14:00:14Z No. of bitstreams: 1 2017_dis_tsfonseca (2).pdf: 4652909 bytes, checksum: 36641c5931a41c244cc0594e09e74d0e (MD5) / Approved for entry into archive by Jairo Viana (jairo@ufc.br) on 2017-08-30T21:27:29Z (GMT) No. of bitstreams: 1 2017_dis_tsfonseca (2).pdf: 4652909 bytes, checksum: 36641c5931a41c244cc0594e09e74d0e (MD5) / Made available in DSpace on 2017-08-30T21:27:30Z (GMT). No. of bitstreams: 1 2017_dis_tsfonseca (2).pdf: 4652909 bytes, checksum: 36641c5931a41c244cc0594e09e74d0e (MD5) Previous issue date: 2017 / The preparation of the antifungal (R)-luliconazole (R-1) and β-agonist (R)-cloroprenaline (R-12 a) drugs and analogues (R-12 b-j) had as key step the preparation of β-halohydrins and β-haloacetates chiral, via kinetic resolution of the corresponding racemic acetates, mediated by lipase. The rac-2-chloro-1-(2,4-dichlorophenyl)ethyl acetate, rac-4 or rac-11 b was used as the "template" substrate to establish the ideal conditions for kinetic resolution via hydrolysis. Through the screening of commercial lipases, were selected the C. antarctica type B, CAL-B, immobilized on acrylic resin (Novozym 435®) and T. lanuginosus (TLL) immobilized on immobead-150, leading to the c values of 50%, e.e.s e e.e.p >92% and E of 185 and 128, respectively. Were evaluated: reaction time, temperature, enzyme/substrate ratio, pH, absence or presence of cosolvents and enzyme reuse. CAL-B was more efficient than TLL, requiring a lower enzyme/substrate ratio (0.5:1) and presenting high activity and selectivity in up to 5 cycles reactions. The best conditions for the resolution of rac-4 were the use of PO43- buffer (pH 7) in the absence of cosolvents, 15 min reaction at 45 °C, leading to c = 50%, e.e.s e e.e.p >99% and E >200. These conditions were used to resolve acetate rac-11 a, which leads to the intermediate in the synthesis of (R)-12 a as well β-haloacetates rac-11 b-j, leading to the analogous (R)-12 b-j. Adjustments in the reaction times were performed (4 h - 9 d) so that the values of c close to 50%. The esters rac-11 a-j were resolved with c ≈ 50%, values of e.e.s and e.e.p = 92 - >99% and E >200. The influence of the esters’ substituents in the time of the kinetic resolution was analyzed considering the steric and electronic effects and evoking the fitting model induced substrate-enzyme with the presence of the hydrophobic pockets. Finally, starting from (S)-2-chloro-1- (2,4-dichlorophenyl)ethanol, (S)-3, (R)-1 was obtained in 43% yield. In order to achieve an atomic economy, we converted the (S)-halohydrins (S)-10 a-j into the respective (R)-acetates (R)-11 a-j via the Mitsunobu reaction, yields ranging from 78-89%. (R)-11 a-j were transformed into the (R)-epoxides (R)-34 a-f; h-j in yields from 68-75% and (R)-11 g was transformed into (R)-halohydrin (R)-10 g in 60% yield. Subsequently, (R)-34 a-f; h-j and (R)-10 g reacted with isopropilamine, yielding (R)-12 a in 71% yield and the analogs (R)-12 b-j in yields 71-80%. Lastly, four imidazole derivatives with yields 72-90% were synthesized, and 1-phenacylimidazole (13) showed antifungal activity against phytopathogenic fungus Fusaruim sacchari, besides the anticorrosive activity for carbon steel. / A preparação dos fármacos antifúngico (R)-luliconazol (R-1) e do β-agonista (R)-clorprenalina (R-12 a) e análogos (R-12 b-j) tiveram como etapa chave a obtenção de β-haloidrinas e β-haloacetatos quirais, via resolução cinética dos correspondentes acetatos racêmicos, mediada por lipase. O rac-acetato de 2-cloro-1-(2,4-diclorofenil)etila, rac-4 ou rac-11 b, foi utilizado como substrato “modelo” para estabelecer as condições ideais para a resolução cinética, via hidrólise. Através da triagem de lipases comerciais, foram selecionadas a C. antarctica do tipo B, CAL-B, imobilizada em resina acrílica (Novozym 435®) e a T. lanuginosus imobilizada em immobead-150 (TLL), as quais levaram a valores de c = 50%, e.e.s e e.e.p >92% e E = 185 e 128, respectivamente. Foram avaliados: tempo reacional, temperatura, razão enzima/substrato, pH, ausência ou presença de cossolventes e reuso das enzimas. A CAL-B foi mais eficiente que a TLL, requerendo uma menor razão enzima/substrato (0,5:1) e apresentando alta atividade e seletividade em até 5 ciclos reacionais. As melhores condições para a resolução de rac-4 foi em tampão PO43- (pH 7) sem cossolventes, 15 min de reação a 45 °C, levando a c = 50%, e.e.s e e.e.p >99% e E >200. Tais condições foram utilizadas para resolver o acetato rac-11 a que leva ao intermediário na síntese da (R)-12 a, bem como dos β-haloacetatos rac-11 b-j, que levam aos análogos (R)-12 b-j. Ajustes nos tempos reacionais foram realizados (4 h - 9 d) para que os valores de c fossem ≈ 50%. Os ésteres rac-11 a-j foram resolvidos com c ≈ 50%, valores de e.e.s e e.e.p = 92 - >99% e E >200. A influência dos substituintes dos referidos ésteres no tempo da resolução cinética foi analisada considerando os efeitos estérico e eletrônico e evocando o modelo do encaixe induzido substrato-enzima com a presença dos bolsões hidrofóbicos. Finalmente, partindo do (S)-2-cloro-1-(2,4-diclorofenil)etanol, (S)-3, foi possível obter o (R)-1 com 43% de rendimento. Objetivando uma economia atômica, convertemos as (S)-haloidrinas (S)-10 a-j nos respectivos (R)-acetatos (R)-11 a-j, via reação de Mitsunobu, com rendimentos de 78-89%. (R)-11 a-f; h-j foram transformados nos (R)-epóxidos (R)-34 a-f; h-j com rendimentos de 68-75% e o (R)-11 g foi transformado na (R)-haloidrina (R)-10 g com 60% de rendimento. Subsequentemente, (R)-34 a-f; h-j e (R)-10 g reagiram com isopropilamina, levando a (R)-12 a com rendimento de 78% e análogos (R)-12 b-j com rendimentos de 71-80%. Por último, foram sintetizados quatro derivados imidazólicos com rendimentos de 72-90%, sendo que o 1-fenacilimidazol (13) apresentou atividade antifúngica frente ao fungo fitopatogênico Fusaruim sacchari, além da atividade anticorrosiva para o aço carbono.

Made available in DSpace on 2016-08-29T15:09:44Z (GMT). No. of bitstreams: 1 tese_3248_Lima Junior 2009.pdf: 1436673 bytes, checksum: 0e58d3c7bd84a8f4c46008c7f6286cb2 (MD5) Previous issue date: 2009-05-22 / As lipases (triacilglicerol acil hidrolases, E.C. 3.1.1.3) são enzimas que atuam no metabolismo microbiano, na hidrólise catalítica de óleos e gorduras por meio de reações de esterificação e transesterificação. Recentemente, estas enzimas foram incluídas em possíveis rotas de produção de biodiesel onde atuam como biocatalisadores no processo de transesterificação. Do ponto de vista do saneamento, a produção de biodiesel pode ser realizada a partir do gerenciamento de resíduos oleosos, os quais, quando convenientemente tratados e processados por via enzimática, podem render significativa produção deste importante biocombustível. O presente estudo teve por objetivo avaliar a biodegradação e atividade lipolítica de cepas bacterianas em resíduos oleosos do saneamento ambiental, representado pela escuma de caixa de gordura, visando à avaliação de sua capacidade hidrolítica em ensaios de bancada. A atividade lipolítica foi avaliada por espectrofotometria, pelo método de respirometria aeróbia e pelo teor de óleos e graxas, utilizando como substratos os resíduos oleosos de caixa de gordura da ETEUFES, do RU-UFES, lodo UASB (5% de óleo de soja) e óleo de fritura. Foram isoladas 24 cepas bacterianas, das quais 18 foram selecionadas pelo método de rodamina-B como bactérias lipolíticas. A atividade lipolítica por espectrofotometria dos isolados evidenciou uma resposta diversificada, variando de 0,02 U/mg a 3,25 U/mg de proteína. A cepa C1 inoculada em meio mínimo com óleo de soja, apresentou valores médios de atividade lipolítica de 3,25 U/mg de proteína. Esta atividade representa cerca de 20% em relação à atividade da enzima comercial utilizada. Nos estudos de respirometria e decaimento de O&G, pode-se observar que, durante o período avaliado, os diferentes potenciais de degradação estão relacionados à atividade lipolítica das cepas por espectrofotometria. As maiores produções de CO2 foram observadas para a lipase comercial, seguida pela cepa C1, variando de 313,64 a 1563,89 mg de CO2. A cepa C1 obteve remoção 87,23% de O&G de combinada com o resíduo de caixa de gordura da ETE-UFES. Desta forma, concluiu-se que há viabilidade em avaliar a atividade lipolítica pelos métodos de respirometria aeróbia e o decaimento de O&G. Palavras-chave: Isolados bacterianos; Lipases; Atividade lipolítica; Respirometria aeróbia.