In this study various microbial and enzymatic methods developed for enantioselective acyloin synthesis for preparation of some pharmaceutically important intermediates. By performing Aspergillus flavus (MAM 200120) mediated biotransformation, enantioselective bio-oxidation of meso-hydrobenzoin was achieved with a high ee value (76%). Racemic form of hydrobenzoin was also employed for the same bio-oxidation process and this bioconversion was resulted in accumulation of meso form (&gt / 90% yield) confirming the suggested mechanism of oxidation-reduction sequence of hydrobenzoin. Wieland-Miescher ketone (3,4,8,8a-tetrahydro-8a-methylnaphthalene-1,6(2H,7H)-dione) is an important starting material for bioactive compounds like steroids and terpenoids. Many synthetic approaches include enantioselective reduction of this compound. In this study Aspergillus niger (MAM 200909) mediated reduction of Wieland-Miescher ketone was achieved with a high yield (80%), de (79%) and ee (94%) value and these results were found much more superior than previously reported studies. Carboligating enzymes benzaldehyde lyase (BAL) (EC 4.1.2.38) and benzoiyl formate decarboxilase (BFD) (E.C. 4.1.1.7) are used for biocatalytic acyloin synthesis. These enzymes are immobilized to surface modified superparamagnetic silica coated nanoparticles by using metal ion affinity technique. With this system recombinant histidine tagged BAL and BFD purified and immobilized to magnetic particles by one-pot purification-immobilization procedure. SDS page analysis showed that our surface modified magnetic particles were eligible for specific binding of histidine tagged proteins. Conventional BAL and BFD catalyzed benzoin condenzation reactions and some representative acyloin reactions were performed with this system with a high enantioselectivity (99-92%) and yield. Results obtained with magnetic particle-enzyme system were also found comparable with that of free enzyme catalyzed reactions.

nÃo hà / O presente trabalho relata a utilizaÃÃo de sementes de gergelim secas e germinadas como fonte de enzimas em reaÃÃes de reduÃÃo, hidrÃlise e esterificaÃÃo. Uma sÃrie de reaÃÃes de reduÃÃo utilizando como biocatalisador sementes de gergelim quimiotipo negra (SGN) foram realizadas, tendo como substratos: acetofenona e derivados halogenados de acetofenona: 2-bromo-acetofenona, 3-bromo-acetofenona, 4-bromo-acetofenona, 2-cloro-acetofenona, 3-cloro-acetofenona, 4-cloro-acetofenona, 2-fluor-acetofenona, 3-fluor-acetofenona, 4-fluor-acetofenona, 2,4-dicloro-acetofenona, 2,4-dibromo-acetofenona e 2,2,2-trifluor-acetofenona. TambÃm foram submetidos à anÃlise derivados de acetofenona substituÃdas com grupos retiradores como, 2-metoxi-acetofenona, 3-metoxi-acetofenona e 4-metoxi-acetofenona e por nitro compostos. TambÃm foram empregadas acetofenonas substituÃdas por grupo amina nas posiÃÃes 2, 3 e 4 do anel aromÃtico. Para vÃrios dos compostos citados, os alcoÃis foram obtidos com bons e excelentes conversÃes (43â99%), a SGN foi enantio e quimiosseletiva, apresentando exelentes excessos enantiomÃricos (80-99%). A segunda parte do trabalho consistiu na utilizaÃÃo do sistema enzimÃtico do gergelim com sementes germinadas (SGG) em reaÃÃes de esterificaÃÃo e na hidrÃlise de Ãsteres. A 1,2-difenil-α-hidroxi-etanona, foi selecionada como substrato padrÃo, em mistura com o agente acilante acetato de vinila, observando como produto o composto identificado como α-acetato de 1,2-difenil-etanona, com um excelente ee ˃99% e conversÃo de 50%. Todos os produtos foram analisados atravÃs de CCD, CLAE, CG-EM e RMN1H e nas determinaÃÃes dos excessos enantiomÃricos utilizou-se CLAE em colunas quirais. / ABSTRACT The present work reports the use of enzyme present in the sesame seeds in the in reduction, hydrolysis and esterification reactions. A series of reactions using as seeds black chemotype extract (SBS) were performed, using selected substrates such as acetophenone and halogenated acetophenones: 2-bromo-acetophenone, 3-bromo-acetophenone, 4-bromo-acetophenone, 2-chloro-acetophenone, 3-chloro-acetophenone, 4-chloro-acetophenone, 2-fluoro-acetophenone, 3-fluoro-acetophenone, 4-fluoro-acetophenone, 2,4-dichloro-acetophenone, 2,4-dibromo-acetophenone and 2,2,2-trifluoro-acetophenone. Experiments were also performed with substituted acetophenone such as 2-methoxy-acetophenone, 3-methoxy-acetophenone and 4-methoxy-acetophenone as well as acetophenones having amine group at C-2, C-3 and C-4 of the aromatic ring. Chiral alcohols were obtained vary from good to excellent yields, in some cases reactions proceeded with chemoselectivity, in others, with enantioselectivity. The second part of research involved the use of the enzyme system of sesame seeds in the esterification and esters hydrolysis. In these reactions were used germinated seeds (GSS) using methodology adapted from the literature. The compound 1,2-diphenyl-α-hydroxy-ethanone were selected as a standard substrate in acetylation reactions. The reactions using vinyl acetate as acylation agent and germinated seeds (GSS) yielded the product identified as α-ethyl- 1,2-diphenyl-ethanone. Optimized parameters were obtained including: amount of seed and substrate, reaction time, solvent, speed and temperature. All products were analyzed by TLC, HPLC, GC-MS and 1H NMR and enantiomeric excess were determined using chiral columns using HPLC.

Les aldéhydes sont des produits chimiques importants dans la synthèse organique, en raison de leurs vastes applications dans les cosmétiques, les produits pharmaceutiques et les herbicides. De plus, ils peuvent être convertis en composés à valeur ajoutée tels que des tensioactifs, des polymères, etc. Classiquement, les aldéhydes sont produits par hydroformylation ou ozonolyse réductrice des alcènes. Cependant, les deux méthodes souffrent de l'utilisation de catalyseurs coûteux et de ligands sophistiqués (hydroformylation) ou de la nécessité d'un procédé à forte intensité énergétique (ozonolyse). En conséquence, le développement d'approches plus durables pour la production d'aldéhydes est hautement souhaitable.Dans ce contexte, nous avons développé deux méthodes pour produire des aldéhydes à partir de dérivés d’acides gras insaturés. La première voie consiste à préparer des a-hydroxycétones grasses à partir de 1,2-diols et les couper pour obtenir des aldéhydes avec de bons rendements. Dans cette voie, deux systèmes catalytiques (homogènes et hétérogènes à base de métaux) ont été développés pour oxyder les diols vicinaux en a-hydroxycétones correspondantes. La coupure de ces espèces a été effectuée par un procédé de rétro-benzoin utilisant des sels de thiazolium thermiquement stables et les aldéhydes ont été récupérés par distillation réactive. La seconde voie repose sur la décomposition des ß-hydroxy hydroperoxydes gras facilement préparés à partir d'oléate de méthyle époxydé. De plus, la décomposition de l'espèce peroxyde a été étudiée dans des conditions thermiques pour donner des aldéhydes. Enfin, la coupure des 1,2-dicétones gras et la valorisation des aldéhydes ont également été étudiés pour conduire aux esters correspondants pouvant être utilisés comme monomères / Aldehydes are important chemicals in organic synthesis, due to their vast applications in cosmetics, pharmaceuticals and herbicides. Moreover, they can be converted to value-added compounds such as surfactants, polymers, etc. Conventionally, aldehydes are produced through hydroformylation or reductive ozonolysis of alkenes. However, both methods suffer from the use of expensive catalyst and sophisticated ligands (hydroformylation) or the requirement of high energy intensive process (ozonolysis). As a result, the development of more sustainable approaches for the production of aldehydes is highly desirable.In this context, we have developed two methods to produce aldehydes from unsaturated fatty acid derivatives. The first route involves the preparation of fatty a-hydroxyketones from 1,2-diols and their cleavage to give aldehydes with good yields. In this route, two catalytic systems (metal-based homogeneous and heterogeneous) have been developed to oxidize vicinal diols to corresponding a-hydroxyketones. The cleavage of these species has been carried out through a retro-benzoin process using thermally stable thiazolium salts and the aldehydes were recovered by reactive distillation. The second route relies on the decomposition of fatty ß-hydroxy hydroperoxides that are easily prepared from epoxidized methyl oleate. Moreover, the decomposition of the peroxide species was studied under thermal conditions to give aldehydes. Finally, the cleavage of fatty 1,2-diketones and the valorization of aldehydes were also studied to give the corresponding esters that could be used as monomers

Cette thèse reporte l'étude expérimentale de la cinétique en phase gazeuse de plusieurs réactions d'intérêt atmosphérique et astrophysique. La connaissance des constantes de vitesse de ces réactions est utile à la compréhension des processus de synthèse et de destruction des molécules dans l'atmosphère terrestre et dans le milieu interstellaire. Sur le plan atmosphérique, nous avons étudié les réactions d'une série d'hydroxycétones, une sous-famille de COV carbonylés, (4-hydroxy-2-butanone, 3-hydroxy-3-méthyl-2-butanone and 4-hydroxy-4-méthyl-2-pentanone) avec le radical OH et l'atome de Chlore Cl afin de définir leur devenir atmosphérique. Nous avons déterminé les constantes de vitesse des réactions de ces hydroxycétones avec le radical OH en absolue à température ambiante et en fonction de la pression en utilisant la cellule cryogénique couplée à la technique PLP-LIF (Photolyse à Laser Pulsé – Fluorescence Induite par Laser). Les constantes de vitesse des réactions de ces hydroxycétones avec Cl ont été mesurées en relative à température ambiante et à pression atmosphérique en utilisant les chambres de simulation atmosphérique couplées aux techniques analytiques de détection : FTIR et GC-MS. En plus, une étude mécanistique a été menée également afin d'identifier et quantifier les produits issus de ces réactions. L'ensemble des résultats obtenus est discuté et nous a permis d'évaluer les implications atmosphériques de ces hydroxycétones (durée de vie et impact sur l'environnement). Le plan astrophysique, la cinétique des réactions impliquant le radical CN et une série de molécules azotées (méthyamine, diméthylamine, triméthylamine et acétonitrile) ont été étudiés sur une large gamme de température (23 K – 354 K) en utilisant la technique CRESU (Cinétique de Réaction en Écoulement Supersonique Uniforme) et la cellule cryogénique couplées à la technique de détection PLP-LIF. Ces études expérimentales ont été accompagnées par des études théoriques afin de mieux comprendre les mécanismes réactionnels. Les éventuelles implications astrophysiques de l'ensemble de ces résultats ont fait l'objet d'une discussion détaillée. / This thesis reports the experimental kinetic study of the gas phase reactions of atmospheric and astrophysical interests. The knowledge of the reactions rate constants is useful to understand the mechanisms of formation and destruction of molecules in the Earth’s atmosphere and in the interstellar medium. On the atmospheric side, we have studied the reactions of a series of hydroxyketones (4-hydroxy-2-butanone, 3-hydroxy-3-methyl-2-butanone and 4-hydroxy-4-methyl-2-pentanone), a large category of hydroxycarbonyls with OH radicals and chlorine atoms Cl in order to determine their atmospheric fate. We have measured the absolute rate constants of the reactions of hydroxyketones with OH radicals by using the cryogenic cell coupled to PLP-LIF technique (Pulsed Laser Photolysis - Laser Induced Fluorescence) at room temperature and as function of pressure. The relative rate constants of the reactions of the compounds investigated with Cl atoms were measured at room temperature and atmospheric pressure by using the atmospheric simulation chamber coupled to the analytical detection techniques: FTIR and GC-MS. In addition, a mechanistic study was also conducted in order to identify and quantify the products formed from these reactions. The whole results are discussed in order to assess the atmospheric implications of these hydroxyketones (lifetimes and environmental impact). On the astrophysical side, the kinetic of the reactions involving CN radical and a series of nitrogen-containing molecules (methylamine, dimethylamine, trimethylamine and acetonitrile) was studied over a wide range of temperature (23 K - 354 K) using CRESU technique (a French acronym standing for Cinétique de Réaction en Ecoulement Supersonique Uniforme) and the cryogenic cell coupled to the detection technique PLP-LIF. These experimental studies were accompanied by theoretical studies to better understand the reaction mechanisms. Possible astrophysical implications of the whole results have been discussed in this study.