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Zastosowanie cieczy jonowych w enzymatycznej syntezie organicznej z wykorzystaniem katalitycznych właściwości lipazy B z candida antarctica

100%

Kołodziejska R. , Jasińska L. , Karczmarska-Wódzka A. , Dramiński M.

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2010

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tom [Z] 64, 5-6

413-434

EN

In organic reactions chemical catalysts as well as catalytic proteins are used. Biocatalysts have become a useful tool for organic chemists, allowing selective, one-step syntheses. Lipases, hydrolytic enzymes, have gained a considerable attention [1]. Lipase-catalyzed reaction proceeds according to the "bi-bi ping-pong" (Scheme 1) [16]. Catalytic potential of lipases allows to obtain a wide range of organic compoundsby formation of C-C, C-N, and C-S bonds [6–8]. Enzyme-catalyzed reactions depend on change of basic-acidic properties or redox potential and an applicationof appropriate solvent can increase the control over chemical balance. The solvent used as the reaction medium should allow enzyme stability, increase its activity and selectivity. In organic hydrophobic solvents, enzyme is more stable and selective, its activity, however, is reduced in comparison to polar solvents [6–8]. During a search for optimal solvent special attention was paid to a typical organic solvents – ionic liquids. Ionic liquids are organic salts (Scheme 2) [9–13]. They do not mix with hydrophobic solvents such as hexane (Tab. 2) [9, 12, 13, 23] and their polarity is similar to low molecular weight alcohols (Tab. 3) [9, 12, 13, 22, 23, 32]. Because of their specific physical properties, ionic liquids may be optimal microenvironment for enzymes, influencing their activity and stability. CALB is widely used in organic syntheses because of its adaptive capability (Tab. 1) as well as regio- and enantioselective properties [18–21]. Due to its exceptional conformation stability in ionic liquids, CALB can be successfully applied both in heterogeneous (Tab. 4) [22, 36] and homogeneous catalysis (Scheme 4, Tab. 5) [37]. The activity of CALB after incubation in ionic liquids is comparable or greater than in conventional organic solvents (Tab. 6, Fig. 1) [9, 13, 23, 38]. A solvent used as a reaction medium should help to maintain enzyme stabilizing its active conformation and protecting it from deactivating factors such as temperature and scCO2 (Tab. 7) [38–43]. Some ionic liquids constitute a bridge between conventional organic solvents and physiological enzyme environment. They provide exceptional activity of catalytic proteins, which allows efficient and selective reaction catalysis (Tab. 8) [6,38–40, 43–61].

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Enancjoselektywna enzymatyczna desymetryzacja katalizowana lipazami. Część II, Optymalizacja warunków reakcji. Związki mezo

88%

Karczmarska-Wódzka A. , Kołodziejska R. , Tafelska-Kaczmarek A. , Przybyła T. , Dramiński M.

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tom [Z] 67, 9-10

819--841

EN

In the enzymatic asymmetric synthesis, the enzyme allows the desymmetrization of achiral compounds resulting in chiral compounds of high optical purity. Meso compounds (bearing a plane of symmetry) are very important group of compounds used in EEDs (Scheme 1) [1–4]. Similarly to prochiral compounds, selective acylation or hydrolysis of meso substrates leads to optically active products. Most lipases preferentially convert the same enantiomers in the above mentioned types of reaction. This allows the preparation of the both enantiomers of the product in high chemical and optical yield (Scheme 3–20) [35–58]. An effective enzymatic catalysis should be performed under conditions optimal for a biocatalyst performance. Hence, it is essential to select an appropriate reaction medium, the pH, and temperature [6–34]. Optimization of the reaction conditions in terms of an appropriate solvent selection is effective and most frequently the simplest way to modify the enzyme selectivity. One of the most important criteria for the solvent selection is its nature [25]. The enzyme selectivity is conditioned by its conformational rigidity, which increases in more hydrophobic medium (typical hydrophobic solvents, scCO2). A hydrophobic solvent decreases biocatalyst lability, which does not allow the connection between the structurally mismatched substrate and the active side of an enzyme [10, 26–31]. Ionic liquids are a separate group of solvents which, despite their high hydrophobicity (logP << 0) and polarity, can constitute an ideal medium for the biotransformation reactions [18–23].

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Prolina – pospolity aminokwas wyjątkowy katalizator. Część II, Międzycząsteczkowa kondensacja aldolowa

88%

Kołodziejska R. , Wróblewski M. , Karczmarska-Wódzka A. , Studzińska R. , Dramiński M.

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tom [Z] 67, 11-12

1027--1050

EN

Proline in organic synthesis is used as a small molecular organocatalyst. In a catalytic act proline, similarly to an enzyme, activates reagents, stabilizes transition state and influences an orientation of substrates [1–12]. Proline works as aldolase I (so called microaldolase I). In comparison with other amino acids it shows exceptional nucleophilicity which makes imines and enamines formation easier. In the intermolecular aldol reaction proline was used for the first time by List and co-workers (Scheme 1) [3, 9, 20]. Since then an immense progress has been observed in this field. Several aldolization reactions were performed in the presence of proline. Reactions of this type proceed between the donor (nucleophile) and the acceptor (electrophile). In aldol reaction the donors can be both ketones and aldehydes which next are condensed with ketones and aldehydes acting as electrophiles (Scheme 2–18; Tab. 1–7) [21–72]. The presence of proline ensures not only high yield of homo- and heteroaldolization but mainly enables conducting enantio- and diastereoselective synthesis. Intermolecular proline-catalyzed aldol condensation proceeds according to enamine mechanism. Anti-aldols, which make a valuable source of intermediates in the synthesis of important biologically active compounds, are mainly obtained in this reaction [35–44, 54, 58, 62, 63, 68, 69, 71].

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Enancjoselektywna enzymatyczna desymetryzacja katalizowana oksydoreduktazami. Reakcje redukcji. Część 2

75%

Kołodziejska R. , Karczmarska-Wódzka A. , Tafelska-Kaczmarek A. , Studzińska R. , Wróblewski M. , Augustyńska B.

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tom [Z] 68, 11-12

1009--1030

EN

Biotransformation reactions of many organic compounds under the influence of enzymes take place with the high selectivity, rarely achieved by other methods. Ketoesters represent an extensive group of selectively bioreduced compounds. Chiral hydroxyesters and, subsequently, hydroxyacids are valuable intermediates in the syntheses of various biologically active compounds. Acyclic α- and β-ketoesters are transformed to the corresponding (R)- and (S)-hydroxyesters by using a specific dehydrogenases. The whole-cells enzymes, e.g. baker’s yeast, may exhibit a different catalytic activity depending on the substrate structure. Baker’s yeast enzymes selectively reduce the cyclic β-ketoesters providing mainly anti diastereomers due to the lack of rotation around the single α,β carbon-carbon bond. The enzymatic reduction of the esters, cyclopentanone, and cyclohexanone derivatives gave the optically active anti-alcohol enantiomers. The reductive EED of prochiral α-ketoesters, as well as β-ketoesters is an interesting transformation in organic chemistry due to the importance of the resulting chiral α-hydroxy acids and their derivatives used as building blocks. Baker’s yeast-catalyzed reduction of alkyl esters derived from pyruvate and benzoylformate allows the preparation of the (R)-alcohols. Polyketones can also be subjected to the reductive EED to give different compounds bearing the quaternary stereogenic centers which are broadly applied in asymmetric synthesis. In asymmetric synthesis, similarly to carbon-oxygen double bonds, carbon-carbon double bonds of prochiral alkanes can be reduced to obtain the optically active saturated compounds. The reduction of alkenes is catalyzed by both, the whole cells (microorganisms, plant cells) as well as isolated enzymes belonging to the oxydoreductases, so-called ene-reductases. The whole-cell catalysts are suitable, most frequently, for the preparative scale syntheses, but they are less chemoselective in comparison to the isolated reductases. In the case of polyfunctionalized alkenes, microorganisms can cause the additional side reaction reducing the desired product yield.

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Enancjoselektywna enzymatyczna desymetryzacja katalizowana oksydoreduktazami. Dehydrogenazy w reakcji redukcji. Część I

75%

Kołodziejska R. , Karczmarska-Wódzka A. , Tafelska-Kaczmarek A. , Studzińska R. , Wróblewski M. , Augustyńska B.

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tom [Z] 68, 9-10

763--782

EN

Enzymes act as biocatalysts whether are also mediating in all anabolic and catabolic pathways, playing an extremely important role in the cells of all life forms. Catalytic potential of oxidoreductases is most commonly used in reduction reactions. Dehydrogenases and reductases catalyze the reversible desymmetrization reactions of meso and prochiral carbonyl compounds and alkenes. The oxidoreductase- catalyzed reactions require cofactors to initiate catalysis. In most cases, it is nicotinamide adenine dinucleotide (NADH) or its phosphorylated derivative (NADPH), which acts as a hydride donor. The necessity of employing expensive cofactors was, for the long time, one of the main limitations to the use of dehydrogenases. This problem was solved by developing a regeneration system of a cofactor in the reaction environment. Various systems are used for the cofactor recycling. In the case of a carbonyl compound reduction, an irreversible oxidation of formic acid to carbon dioxide is most frequently used. In this paper, selected examples of whole-cell and isolated enzymes applications in the carbonyl compound reduction are discussed. The application of baker’s yeast, microorganisms and dehydrogenases in enantioselective enzymatic desymmetrization (EED) of prochiral ketones leads to a broad spectrum of chiral alcohols used as intermediates in the syntheses of many pharmaceuticals and compounds presenting a potential biological activity.