Nesta dissertação de mestrado foram estudadas duas bactérias, Sphingobacterium sp e Arthrobacter atrocyaneus, produtoras de enzimas álcool desidrogenases que se mostraram capazes de catalisar reações de oxidação enantiosseletiva de alcoóis secundários racêmicos. Inicialmente foram avaliados alguns parâmetros para a realização da resolução cinética do (RS)-1-feniletanol, assim como quantidade de substrato, biomassa das bactérias (Sphingobacterium sp e Arthrobacter atrocyaneus) e tempo reacional necessário para a oxidação completa de um dos enantiômeros do substrato. Nas reações com a bactéria Sphingobacterium sp (R1AC23) observou-se a presença de álcool desidrogenase com alta atividade catalítica, porém com moderada enantiosseletividade, pois em alguns casos observou-se a oxidação completa dos alcoóis para-substituídos derivados do (RS)-1- feniletanol a suas correspondentes cetonas. Com o estudo das reações do (RS)-1-feniletanol e a bactéria Arthrobacter atrocyaneus (R1AF57) determinou-se os principais parâmetros reacionais para alcançar uma excelente resolução cinética. Sendo assim, aplicou-se essa metodologia para diferentes alcoóis secundários em dois meios reacionais diferentes: com células em crescimento e com células ressuspensas em tampão fosfato. A atividade catalítica foi mais eficiente com as células em crescimento com conversões próximas de 50% e excesso enantiomérico >99% na maioria dos casos, destacando-se os derivados do (RS)-1-feniletanol para e meta substituídos. Empregou-se a Arthrobacter atrocyaneus em testes de resolução cinética dinâmica (RCD). Como durante as reações de oxidação um co-produto é uma cetona, estudou-se o emprego in situ do NaBH4 como redutor desse composto. Com isso, tem-se um ciclo reacional de oxidação-redução. Sendo assim, por estereoinversão, foi possível alcançar rendimentos maiores que 50% do álcool enantiomericamente puro. Com o (RS)-1-(4-metilfenil)-etanol como substrato, obteve-se o álcool enantiomericamente puro com rendimento de 79% e excesso enantiomérico >99% / In this dissertation two bacterial strains were studied, Arthrobacter atrocyaneus and Sphingobacterium sp, which are alcohol dehydrogenases producers that were able to catalyse racemic secondary alcohols enantioselective oxidation. Initially, some reaction parameters to carry out the kinetic resolution of (RS)-1- phenylethanol were evaluated, such as substrate amount, bacterial biomass (Arthrobacter atrocyaneus and Sphingobacterium sp) and the reaction time for complete oxidation of one enantiomer of the substrate. In the reactions with Sphingobacterium sp (R1AC23) was observed the presence of alcohol dehydrogenase with high catalytic activity and moderate selective. Therefore, in some cases, the total oxidation of the both enantiomers of (RS)-1- phenylethanol para-substitued derivatives to the corresponding ketones were observed. By studying the reactions of (RS)-1-phenylethanol and Arthrobacter atrocyaneus (R1AF57), the reaction parameters to achieve excellent kinetic resolution were determined. Therefore, this methodology was applied to different secondary alcohols under two different reaction media: with growing cells and resting cells in phosphate buffer. The catalytic activity was more efficient with growing cells. The conversions were next to 50% and enantiomeric excess> 99% in most of the cases, especially those reactions with alcohols derived from (RS)- 1-phenylethanol para and meta substituted. Arthrobacter atrocyaneus was employed in dynamic kinetic resolution (DKR). As during the oxidation reactions, a ketone co-product is obtained, the use of NaBH4 was studied to reduce this compound in situ. Thus, an oxidation-reduction reactional cycle was achieved. Then, by estereoinversion it was possible to achieve yields higher than 50% of the pure enantiomerically alcohol. With (RS)-1-(4-methylphenyl)-ethanol as substrate, enantiomeric excess > 99% and yield 79% of pure enantiomerically alcohol was obtained

Neste trabalho prepararam-se ésteres de ácidos graxos por esterificação do ácido oléico e transesterificação do óleo de soja e do triéster oléico via catálise enzimática. Determinou-se a composição dos produtos obtidos por RMN 1H e CG-FID. Os padrões dos ésteres do ácido oléico via esterificação ácida foram preparados empregando ácido sulfúrico, os padrões dos ésteres do óleo de soja por transesterificação básica com hidróxido de sódio e o padrão do triéster oléico foi sintetizado utilizando ácido p-tolueno sulfônico como catalisador. A melhor enzima para essas reações foi determinada através de reações de esterificação do ácido oléico e transesterificação do óleo de soja com etanol na ausência de co-solventes, sendo que foi selecionada a lipase de Candida antarctica. A mesma enzima foi empregada nas esterificações enzimáticas do ácido oléico com diversos alcoóis (metanol, etanol, n-propanol e n-butanol), na transesterificação enzimática do óleo de soja e do triéster oléico com etanol. Em ambos os estudos, foram avaliados os fatores que influenciam as reações: quantidade de enzima; tempo de reação; água adicionada ao álcool e reuso do biocatalisador. Na esterificação enzimática do ácido oléico, o uso do etanol forneceu o melhor rendimento (96,5%) com 5,0% (m/m) de enzima em 24 horas de reação. Quando uma quantidade de 4,0% de água foi adicionada ao álcool, a reação utilizando metanol mostrou maior eficiência (98,5%) e os rendimentos com os outros alcoóis não foram alterados significativamente (acima de 90%). Também foi possível utilizar a enzima por até 10 ciclos sem perda de rendimento, com exceção do metanol, onde ocorreu um decréscimo acentuado de rendimentos nos ciclos seguintes. Na transesterificação enzimática do óleo de soja, os mesmos fatores foram avaliados e com 5,0% de enzima, após 24 horas, foi obtido um rendimento de 84,1% e com a adição de água o rendimento não foi significativamente alterado (83%). Na transesterificação, os métodos de quantificação por RMN 1H e CG-FID foram comparados sendo que uma maior diferença foi observada para as reações com baixos rendimentos por RMN 1H, porém em altos rendimentos a diferença entre os dois métodos não foi significativa. Monoglicerídeos e diglicerídeos foram quantificados por CG-FID e por RMN 1H onde foi possível calcular a razão dos produtos formados através de uma equação desenvolvida, sendo que a diferença entre esses tipos de análises foi pequena, de apenas 1,4%. A transesterificação enzimática do triéster oléico foi obtida em bom rendimento (90,4%) e uma pequena quantidade de mono- e diglicerídeos foi produzida. Em todas as reações de transesterificação, o glicerol não foi detectado após a lavagem dos produtos. A metodologia empregando a lipase de Candida antarctica mostrou-se eficiente para a produção de biodiesel a partir do óleo de soja e do ácido oléico com diferentes tipos de alcoóis. / In this work, it was prepared esters of the fatty acid by esterification of the oleic acid and transesterification of the soy oil through enzymatic catalysis. It was determined the composition of the products obtained by 1H NMR and GC-FID. The standards of esters of the oleic acid by acid esterification was prepared employing sulfuric acid, the standards of esters of the soy oil by alkaline transesterification with sodium hydroxide and the standard of the oleic triester was synthesized employing p-toluene sulfonic acid as catalyst. The best enzyme for those reactions was determined through reactions of esterification of the oleic acid and transesterification of the soy oil with ethanol and free co-solvents, and lipase from Candida antarctica was selected. The same enzyme was employed in the enzymatic esterifications of the oleic acid with various alcohols (methanol, ethanol, propanol and butanol), in the enzymatic transesterification of soy oil and the oleic triester with ethanol. In both studies, was assessed the factors that influence the reactions: amount of catalyst, reaction time, water added in the alcohol and the turnover of biocatalyst. In the enzymatic esterification of the oleic acid, the ethanol showed the better yield (96,5%) with 5,0% (m/m) of enzyme at 24 hours of reaction. When 4,0% of water was added to the alcohol, the methanol showed the high efficiency (98,5%) and the yield with another alcohols were not affected. It was also possible to use the enzyme for 10 cycles without lose yield, except for the methanol. In the enzymatic transesterification of the soy oil, the same factors were assessed using 5,0% of enzyme, after 24 hours, a yield of 84,1% was obtained and with the water addition the yield was not modified (83%). On the transesterification, 1H NMR and GC-FID were compared and a great difference was observed for low yields, but on high yields, the difference between methods was small. Monoglycerides and diglycerides were quantified by GC-FID and detected by 1H NMR, it was possible to calculate the ratio between them on the products formed through an equation developed and the difference for this type of analysis was small, only 1.4% . The enzymatic transesterification of the oleic triester was obtained with good yield (90,4%) and a small amount of the monoglycerides and diglycerides was produced. In all the transesterifications reactions, glycerol was not detected after washing mixture of products. The methodology employing Candida antarctica lipase was efficient for biodiesel production by soybean oil and oleic acid with different alcohols.

The asymmetric reduction of ketones to chiral hydroxyl compounds by alcohol dehydrogenases (ADHs) is an established strategy for the provision of valuable precursors for fine chemicals and pharmaceutics. However, most ADHs favor linear aliphatic and aromatic carbonyl compounds, and suitable biocatalysts with preference for cyclic ketones and diketones are still scarce. Among the few candidates, the alcohol dehydrogenase from Thauera aromatica (ThaADH) stands out with a high activity for the reduction of the cyclic α-diketone 1,2-cyclohexanedione to the corresponding α-hydroxy ketone. This study elucidates catalytic and structural features of the enzyme. ThaADH showed a remarkable thermal and pH stability as well as stability in the presence of polar solvents. A thorough description of the substrate scope combined with the resolution and description of the crystal structure, demonstrated a strong preference of ThaADH for cyclic α-substituted cyclohexanones, and indicated structural determinants responsible for the unique substrate acceptance.

No description available.

Une organisation contrôlée de la porosité offre l’opportunité de combiner les avantages structuraux des macropores (diamètres supérieures à 50 nm), assurant l’intégrité et l’interconnectivité de l’ossature du matériau, avec ceux des pores plus étroits (méso- et micropores), déployant des surfaces spécifiques réactives importantes. L’élaboration de telles architectures, dites « hiérarchisées », à l’échelle du laboratoire représente un véritable défi physico-chimique. Dans ce contexte, ce travail de thèse s’intéresse à l’élaboration de matériaux poreux fonctionnels avancés, s’inscrivant dans le concept de chimie intégrative, en combinant matière molle (mésophases lyotropes, émulsions directes concentrées, auto-assemblages organique-organique, etc.), procédé sol-gel, polymérisation organique et principe de l’empreinte « dure ». Dans une première approche générale, des monolithes hybrides macrocellulaires à base de silice ont été fonctionnalisés par greffage covalent post-synthèse ou par co-condensation de précurseurs organosilanes appropriés. Dès lors, l’encapsulation de complexes luminescents (ions europium), de catalyseurs métalliques piégés dans une phase liquide ionique supportée (sels ou nanoparticules de palladium), ou d’entités biologiques (enzymes hydrosolubles : lipases) a offert une modulation rationnelle des propriétés optiques, catalytiques ou biocatalytiques induites in fine. Dans une seconde approche générale, l’utilisation de monolithes de silice macrocellulaires comme empreintes dures « sacrificielles » a permis la genèse de composés carbonés poreux, associée à un contrôle structural sur plusieurs échelles. Dès lors, une surface spécifique développée et une porosité hiérarchisée, conjuguées à des propriétés intrinsèques opportunes (stabilités thermique et chimique, conductivité électrique), ont offert un large champ d’applications, comme électrodes pour systèmes de stockage de l’énergie électrochimique (batteries Li-ion et condensateurs à double couche électrochimique), sites de nucléation de borohydrures de lithium (LiBH4) pour le stockage de l’hydrogène, ou encore comme électrodes enzymatiques pour biopiles. / Mainly induced by the wide scope of expected applications, designing hierarchical porous architectures appears today as a strong and competitive field of research. The opportunity to combine the structural advantages of both macropores (diameters larger than 50 nm), providing interconnected framework while reducing the diffusion low kinetic issue, with those of the more narrow pores (meso and micropores), generating high surface reactive areas, has induced a need for novel synthetic routes to achieve hierarchical structures. In this view, by combining soft mater (lyotropic mesophases, concentrated direct emulsions or organic-organic self-assemblies, etc.), sol-gel process, organic polymerization and hard-template approaches, we have generated new functional porous materials, fitting with the transversal integrative chemistry concept. In a first general approach, organically grafted silica foams have been designed, either by a grafting method or a one-pot co-condensation route of organosilane derivatives, to encapsulate luminescent complexes (europium ions), metallic catalysts entrapped into supported ionic liquid phase (palladium salts or nanoparticules) or bio-related entities (water-soluble enzymes: lipases), dealing with promising optical, catalytic or biocatalytic properties. In a second synthetic pathway, using siliceous foams as “sacrificial” hard templates, carbonaceous foams have been obtained addressed through a structural design over several length scales. Due to inherent high surface area, chemical inertness, thermal stability and good conductivity, this new foams series has offered a large field of applications, such as electrodes for electrochemical energy storage devices (Li-ion batteries and electrochemical double-layer capacitors), host sites for hydrogen storage through LiBH4 nucleation, as well as advanced porous electrodes for enzyme-based biofuel cells.

Les céramides sont des lipides de la classe des sphingolipides issus de la N-acylation d’une base sphingoide par un acide gras. Ces lipides et leurs analogues suscitent un grand intérêt comme composants actifs dans les industries pharmaceutique et cosmétique. Parmi les biocatalyseurs capables de réaliser la synthèse de ce type de lipide, la lipase B de Candida antarctica semble être l’enzyme la plus adaptée à la production de « pseudo-céramides » à partir d’amino-polyols. Dans ce contexte, nous avons abordé l’étude de l’acylation de composés de type « amino-alcool »catalysée par la lipase B de Candida antarctica, en gardant à l'esprit une approche fondamentale afin d’élargir les connaissances actuelles sur ce sujet. La première partie de notre travail a ainsi traité de l’étude cinétique de l’acylation de composés monofonctionnels afin de déterminer les mécanismes réactionnels et l’énantio sélectivité de la lipase B de Candida antarctica pour les réactions de N-acylation et de O-acylation. Les parties suivantes de notre travail ont porté sur une étude structure-réactivité du substrat accepteur d’acyle et sur l’étude de l’influence du solvant utilisé (solvant organique ou liquide ionique) afin de déterminer les facteurs clés influençant la chimio sélectivité et la régio sélectivité de la lipase B de Candida antarctica lors de l’acylation de composés multifonctionnels de type « amino-alcool ». Finalement, à partir des connaissances acquises dans les différentes parties, nous avons développé et optimisé un procédé de synthèse enzymatique de « pseudo-céramides » (O,N-diacyl aminopropanediols) mis en oeuvre en réacteur continu à « lit fixe ». / Ceramides are lipids from the sphingolipide class derived from the N-acylation of a sphingoid base from a fatty acid. These lipids and their analogs are compounds of interest used as active components in pharmaceutical and cosmetic industries. Among biocatalysts able to synthesize this type of lipids, Candida antarctica lipase B appears to be the most appropriate enzyme for the production of "pseudo-ceramides" derived from amino-polyols. In this context, we have studied the acylation of amino-alcohol-like compounds catalyzed by Candida antarctica lipase B, keeping inmind a fundamental approach to expand the current knowledge on this subject. The first part of our work aimed to determine the reaction mechanisms and the enantio selectivity exhibited by Candida antarctica lipase B during O-acylation and N-acylation reactions, by conducting a kinetic study of mono functional compound acylation. In the following parts of our work, we performed a structurere activity study of the acyl acceptor substrate and evaluated the effect of the solvent used (organic solvent or ionic liquid) to determine the key factors influencing the chemo selectivity and the regio selectivity of the Candida antarctica lipase B-catalyzed acylation of polyfunctional amino alcohol compounds. Finally, starting from the knowledge acquired in the previous parts, we have developed and optimized an enzymatic process of “pseudo-ceramide” (O,N-diacylaminopropanediol) synthesis performed in a continuous packed-bed reactor.

L'oxydation de Baeyer-Villiger (BV) par voie enzymatique est une méthode efficace pour obtenir de lactones sous forme énantiomériquement pure. Les Baeyer-Villiger Monooxygénases (BVMO) sont ainsi capables d'oxyder de nombreux substrats avec une stéréospécificité remarquable.Nous avons recherché de nouvelles enzymes dans le génome de deux souches appartenant au genre Acinetobacter, A. baylyi ADP1 et A. baumannii AYE. Six gènes ont été clonés dans E. coli. Leur profil de substrat a été étudié en utilisant des cellules entières de ce microorganisme recombinant comme biocatalyseur. Quatre enzymes ont montré une spécificité de substrat similaire, avec une préférence pour les petites cétones cycliques et pour les substituants aryliques. Une de ces enzymes a permis le Dédoublement Cinétique Parallèle Régiodivergent d'une bicyclohepténone et la désymétrisation de cyclobutanones benzyliques avec, dans chaque cas, une énantiosélectivité intéressante car conduisant à des énantiomères rarement obtenus par réaction de BV enzymatique.Dans une seconde partie, des Dédoublements Cinétiques Dynamiques, associant réaction de BV enzymatique et racémisation in situ ont été réalisés avec des cellules entières d'E. coli produisant la Cyclohexanone Monooxygenase (CHMO) issue d'A. calcoaceticus. La racémisation de cyclohexanones α-substituées, habituellement difficilement racémisables, a été assurée par l'emploi de solutions tampons à base de sels de phosphate ou de glycine. Les -caprolactones correspondantes ont été isolées sous forme d'esters méthyliques hydroxylés quasi énantiopurs avec des rendements compris entre 70 et 80%. / Enzyme-mediated Baeyer-Villiger oxidation is nowadays largely recognized as an efficient method to obtain highly optically active lactones. An increasing number of Baeyer-Villiger Monooxygenases from various sources has been found to oxidize a large range of substrates with a good to excellent stereospecificity.Firstly, in order to enlarge the scope of these biotransformations, the genome of two strains of the Acinetobacter genus, A.baylyi ADP1 and A.baumannii AYE was explored. Six genes were expressed in E. coli and the substrate profile of each enzyme was studied using whole cell biotransformations. Four enzymes showed close substrate specificity with a preference for small cyclic ketones and for arylic substituents. Interestingly, one enzyme led to a Kinetic Parallel Regiodivergent Resolution of a bicycloheptenone and desymmetrisation of benzylic cyclobutanones in an enantiocomplementary manner when compared to the most of already known enzymes.The second part of this work describes the implementation of Dynamic Kinetic Resolution processes combining enzymatic BV oxidation and in situ racemization of α-substituted cyclohexanones to afford corresponding lactones in more than 50% yield. Cyclohexanone Monooxygenase (CHMO) from another Acinetobacter strain, A. calcoaceticus, was selected and the reactions were carried out with whole cells of producing CHMO E. coli strain. The racemization of α-substituted cyclohexanones, usually slowly racemized under basic conditions, was ensured by the use of containing phosphate salts or glycine buffer solutions. Several corresponding -caprolactones were isolated after methylation as enantiopure hydroxy methyl esters in 70-80% yield.

Ce travail développe différentes stratégies pour la synthèse énantiosélective de sesquiterpènes naturels à partir de chirons obtenus par biocatalyse. La première partie est consacrée aux premières synthèses énantiosélectives de la kopéoline, et de la kopéolone. La synthèse de la structure décrite de la kopéoline est réalisée, les composés ont été entièrement caractérisés. Les résultats montrent que les structures reportées n'ont pas été correctement assignées, et suggèrent une mauvaise attribution des stéréocentres au cours de l'isolement des produits naturels. Ainsi, deux nouvelles structures sont proposées. Les synthèses totales de ces deux dernières structures ont également été réalisées et ont permis de confirmer la révision structurelle et de caractériser complètement ces produits naturels tout en élucidant leurs configurations absolues inconnues jusqu'alors.La seconde partie aborde la synthèse du siphonellinol D selon une méthodologie convergente d'une partie Est et d'une partie Ouest. Les deux énantiomères d'un chiron ont été obtenus par dédoublement cinétique enzymatique avec des rendements élevés et d'excellentes énantiosélectivités. À partir de l'énantiomère (1S, 6R), la synthèse de la partie Est est rapportée. Malheureusement, une première méthodologie employant l'énantiomère (1R, 6S) n'a pas permis l'obtention de la partie bicyclique Ouest. Une seconde méthodologie utilisant le géraniol comme substrat a permis l'accès à la partie Ouest du siphonellinol D sous forme racémique. Une réaction de couplage entre ces deux parties a été réalisée avec succès permettant d'envisager de manière optimiste la synthèse du siphonellinol D par ce chemin synthétique. / This work deals with different strategies used in the course of the enantioselective synthesis of natural sesquiterpenes starting from an enantiopure building block obtained by biocatalysis. The first part is dedicated to the first enantioselective syntheses of kopeolin, and kopeolone. The synthesis of kopeolin was achieved and compounds have been fully characterized. The results showed that the reported structures were not assigned correctly, and suggest an initial structural misassignment during the isolation of the natural products. Thus, two new structures for kopeolin and for kopeolone are proposed. The enantioselective total syntheses of these two proposed structures have been achieved and permitted to confirm the structural revision and to fully characterize these natural products while elucidating their hitherto unknown absolute stereochemistries.The second part is dedicated to the synthesis of siphonellinol D with a convergent methodology of the Eastern part and the Western part. Both enantiomers of this building block were obtained by an enzymatic kinetic resolution in high yields and excellent enantioselectivities. Starting from the (1S, 6R) enantiomer, the synthesis of the Eastern part of Siphonellinol D is reported. Unfortunately, a first methodology using the use of the (1R, 6S) enantiomer failed. A second methodology using geraniol as starting material led to the racemic Western part of siphonellinol D. A coupling reaction were successfully performed allowing us to consider the synthesis of siphonellinol D by this synthetic pathway as optimistic.

O trabalho teve por objetivo principal estudar a reação de hidroteluração de 3-hidróxialcinos (álcoois propargílicos), levando à preparação enantiosseletiva de teluretos vinílicos Z funcionalizados com uma hidroxila. Tais sistemas são interessantes do ponto de vista sintético, uma vez que muitas moléculas de interesse biológico possuem duplas ligações associadas a hidroxilas em sua estrutura. Inicialmente, alguns dos álcoois propargílicos foram preparados em laboratório (Esquema IA) e, em seguida, submetidos à reação de hidroteluração (Esquema IB). (Ver no arquivo). Como resultado da hidroteluração de álcoois propargílicos, obteve-se uma mistura de regioisômeros 1,2-dissubstituído e 1,1-dissubstiuído, sendo que a proporção entre eles variou de acordo com o substituinte R (Tabela I). (Ver no arquivo). Observou-se que quanto mais volumoso o grupo R, maior foi a quantidade do isômero 1,2-dissubstituído (telureto vinílico de interesse) obtida. Assim, decidiu-se proteger os álcoois propargílicos com grupos protetores volumosos e submetê-Ios à reação de hidroteluração, sendo os resultados obtidos bastante satisfatórios (Tabela II) . (Ver no arquivo). Os melhores resultados foram obtidos ao se proteger a hidroxila com o grupo t-butildimetilsilila (TBDMS), na forma de éter de silício e cabe ressaltar que em alguns casos apenas o telureto vinílico de interesse foi obtido. Em seguida, foram feitas diversas tentativas de desproteger os teluretos vinílicos obtidos empregando sais de flúor, mas não foram obtidos resultados satisfatórios, uma vez que não foi possível obter o telureto com a hidroxila desprotegida. No entanto, os resultados obtidos foram muito interessantes, pois pode-se concluir que a regiosseletividade da reação de hidroteluração depende de fatores esféricos e pode ser controlada. Além disso, foram obtidos enantiosseletivamente teluretos vinílicos Z, que representam blocos de construção interessantes para aplicação em síntese orgânica. / This project consisted in studying the main characteristics of the hidrotelluration reation of 3-hydroxy alkynes (propargylic alcohols), which lead to the enantiosselective preparation of Z-vinyl tellurides. Such structures are quite interesting for organic synthesis, due to the fact that a large nurnber of biologically relevant compounds contains Z double bonds and hydroxyl groups. Firstly, propargylic alcohols were prepared (Scheme IA) and submitted to hidrotelluration reation (Scheme IB). (See file). The formation of two isomers was observed as a result of the hydrotelluration of 3-hydroxy alkynes. The ratio between 1,2-disubstituted and 1,1-disubstituted isomers showed to be dependent on the group (R) present in the alkyne structure (Table I). It was observed that more hindered groups lead to the formation of a larger amount of 1,2-disubstituted derivative (desired vinyl telluride). So, the 3-hydroxy alkynes were protected with hindered groups and submited to hydrotelluration reaction (Table II). (See file) The use of TBDMS as protective group generated the best results and it is noteworthy that for some alkynes only the desired vinyl telluride was obtained. The results were interesting and it is noteworthy that in some cases only the desired vinyl telluride was obtained. In the following step, several tries to desprotect the hydroxyl group were perfomed, by the use of diferent fiuorine salts, but it was not possible to obtain the free hydroxyl group. Even though, relevant results were observed because it was possible to conclude that the regiosseiectivity of hudrotelluration reaction is sensitive to steric effects and can be controlled. Besides that, a convenient method for the enantiosselective preparation of Z vinyl tellurides was described, wihch are interesting building blocks for organic synthesis.

Neste trabalho, enzimas álcool-desidrogenases provenientes de fungos marinhos e a lipase imobilizada de Candida antarctica foram utilizadas para produção de compostos de interesse sintético e biológico. No capítulo 1, enzimas álcool-desidrogenases de fungos isolados da alga marinha Bostrychia radicans foram empregadas em reações de redução de cetonas fluoradas 1-5. Os fungos identificados como Botryosphaeria sp. CBMAI 1197, Eutypella sp. CBMAI 1196, Hidropisphaera sp. CBMAI 1194 e Xylaria sp. CBMAI 119 atuaram como biocatalisadores nestas reações levando à produção de álcoois com elevada pureza enantiomérica. O fungo Botryosphaeria sp. CBMAI 1197 destacou-se frente aos demais microrganismos, produzindo os álcoois (S)-2,2,2-trifluoro-1-feniletanol (1a) e (R)-1-(2,4,5-trifluorofenil)etanol (3a) com excelentes conversões (100% e 97%) e excessos enantioméricos (ee >99%). Este fungo também apresentou enzimas álcool-desidrogenases ativas frente a cetonas dicarboniladas 4-5, produzindo os álcoois 4,4,4-trifluoro-1-fenil-1,3-butanodiol (4a) e 4,4,4-trifluoro-1-(2-naftalenil)-1,3-butanodiol (5a) com 100% de conversão em ambos os casos e com purezas enantioméricas respectivas a 99% e 97%. Este foi o primeiro estudo realizado no Brasil com fluorocetonas dicarboniladas e com os fungos isolados da alga marinha Bostrychia radicans. No capítulo 2, a lipase comercial de Candida antarctica foi o biocatalisador empregado em reações de aminólise entre os ésteres linoleato de etila (1) e salicilato de etila (3), a amina graxa N-dodecilamina (2) e os aminoálcoois (4-9). A amina graxa N-dodecilamina (2) também foi utilizada em reações com o linoleato de etila (1), onde a lipase de Candida antarctica produziu a respectiva amida graxa 10 com rendimentos superiores a 95%. Os aminoálcoois foram selecionados para reações com o salicilato de etila (3), onde a lipase exibiu quimiosseletividade pelo grupo amino, produzindo predominantemente amidas fenólicas (12-19) com rendimentos entre 23-68%. A enzima CALB apresentou quimiosseletividade reduzida na reação com o 5-aminopentanol (6) onde os produtos amida 14 e éster 15 foram obtidos com rendimentos de 44 e 33%, respectivamente. O produto 2-hidroxi-N-(2-hidroxipropil)benzamida (19) foi obtido com rendimento superior a 90% a partir da reação catalisada pela lipase de Candida antarctica. Este produto foi selecionado como intermediário para a síntese de uma molécula hidrofóbica 21 que apresenta o éster oleato de etila em sua constituição. O produto 21 foi obtido com 75% de rendimento. As amidas fenólicas 12-21 produzidas neste trabalho são derivadas do ácido linoleico (ômega 6) e do ácido salicílico, os quais apresentam propriedades emolientes e antioxidantes. Estes compostos são interessantes para a formulação de produtos cosméticos de aplicação cutânea. Neste processo biotecnológico as reações foram conduzidas na ausência de solventes orgânicos, evitando o tratamento de solventes voláteis e a formação de subprodutos. Os compostos foram analisados por Cromatografia líquida de alta eficiência e caracterizados por RMN (1H, 13C), EMAR e IV. A aplicação de reações de biocatálise seja através de células microbianas ou de enzimas isoladas foram muito promissoras na síntese de compostos orgânicos de interesse como álcoois enantiomericamente puros ou amidas graxas. / In this work, alcohol dehydrogenase (ADHs) enzymes from marine fungi and immobilized lipase from Candida antarctica were employed for the production of compounds of biological and synthetic interest. In chapter 1, ADHs of fungi isolated from the marine alga Bostrychia radicans were used in reduction reactions of fluorinated ketones 1-5. The fungi identified as Botryosphaeria sp. CBMAI 1197, Eutypella sp. CBMAI 1196, Hidropisphaera sp. CBMAI 1194 and Xylaria sp. CBMAI 119 acted as biocatalysts in these reactions leading to production of alcohols with high enantiomeric purity. The fungus Botryosphaeria sp. CBMAI 1197 presented highlighted compared to other microorganisms producing the alcohols (S)-2,2,2-trifluoro-1-phenylethanol (1a) and (R) -1 - (2,4,5-trifluorophenyl) ethanol (3a) with excellent conversions (100% and 97%) and enantiomeric excesses (ee > 99%). This fungus also exhibited ADHs enzymes active with dicarbonylateds ketones, leading to the production of the alcohols 4,4,4-trifluoro-1-phenylbutane-1,3-diol (4a) and 4,4,4-trifluoro-1-(naphthalen-2-yl)butane-1,3-diol -1,3-butanediol (5a) with conversions of 100% in both cases and enantiomeric excess of 99%-97%, respectively. This was the first study conducted with dicarbonilated fluoroketones 4-5 and with fungi isolated from the marine alga Bostrychia radicans in Brazil. In chapter 2, immobilized lipase from Candida antarctica was used as biocatalyst in the aminolysis reaction between esters of ethyl linoleate (1) and ethyl salicylate (3), the fatty amine N-dodecylamine (2) and the aminoalcohols (4-8). Six aminoalcohols were selected for reactions with ethyl salicylate (3), where the lipase exhibited chemoselectivity by the amino groups, producing predominantly phenolic amides in yields of 23-63%. The CALB exhibited um reduction in chemoselectivity in the reaction with 5-aminopentanol (6) where the amide 14 and ester 15 products were obtained with 44% and 33% yields. The product 2-hydroxy-N-(2-hydroxypropyl) benzamide (19) was obtained in yield greater than 90% from the reaction catalyzed by lipase from Candida antarctica. This product was selected as reagente for the synthesis of a hydrophobic molecule 21 presenting ester ethyl oleate in its constitution. The product 21 was obtained in 75% yield. The phenolic amides 12-21 produced in this work are derived from linoleic acid (omega 6) and salicylic acid, which presents emollient and antioxidants properties. These compounds are interesting for the formulation of cosmetic products for skin application. In this biotechnological process, the reactions were carried out under solvent-free conditions and vacum, avoiding the treatment of volatile solvents and by-product formation. The compounds were analyzed by high performance liquid chromatography and characterized by NMR (1H, 13C), IR and HRMS. Applying biocatalysis reactions, either through microbial cells or isolated enzymes were promising for the synthesis of organic compounds such as enantiomerically pure alcohols and fatty phenolic amides.