Peroxidases, asymmetric oxidation

Okrasa and co-workers reported an interesting combination reaction of glucose oxidase and peroxidase in a mixed solvent of [bmimJpFg] with water (Fig. 18). Asymmetric oxidation of sulfide was accomplished successfully in the reaction system. ... 

Optically active epoxides are important building blocks in asymmetric synthesis of natural products and biologically active compounds. Therefore, enantio-selective epoxidation of olefins has been a subject of intensive research in the last years. The Sharpless [56] and Jacobsen [129] epoxidations are, to date, the most efficient metal-catalyzed asymmetric oxidation of olefins with broad synthetic scope. Oxidative enzymes have also been successfully utilized for the synthesis of optically active epoxides. Among the peroxidases, only CPO accepts a broad spectrum of olefinic substrates for enantioselective epoxidation (Eq. 6), as shown in Table 8. 

Oxometalloporphyrins were taken as models of intermediates in the catalytic cycle of cytochrome P-450 and peroxidases. The oxygen transfer from iodosyl aromatics to sulfides with metalloporphyrins Fe(III) or Mn(III) as catalysts is very clean, giving sulfoxides, The first examples of asymmetric oxidation of sulfides to sulfoxides with significant enantioselectivity were published in 1990 by Naruta et al, who used chiral twin coronet iron porphyrin 27 as the catalyst (Figure 6C.2) [79], This C2 symmetric complex efficiently catalyzed the oxidation... 

Scheme 53. Horseradish peroxidase-mediated asymmetric oxidative dimerization of 2-naphthol (68a).

The focus is on proteins with redox functionalities hke oxidases, mono- and dioxygenases, and other enzymes able to utilize molecular oxygen as an oxidant, but dehydrogenases and peroxidases will also be discussed. The use of common proteins such as bovine serum albumin with no distinctive redox functionalities as chiral templates for asymmetric oxidations has been reviewed elsewhere [16]. As the oxidations require the transfer of electrons from a substrate to an electron... 

Biocatai ftic Asymmetric Oxidations with Peroxidases 319... 

As enantiomericaUy pure sulfoxides are excellent chiral auxUiaries for asymmetric synthesis, different approaches for biocatalytic asymmetric oxidations at the S-atom have been explored [30, 31]. Asymmetric peroxidaseorganic sulfides to sulfoxides in organic solvents opens up attractive opportunities by increased substrate solubility and diminished side reactions [32]. Plant peroxidases located in the cell wall are capable of oxidizing a broad range of structurally different substrates to products with antioxidant, antibacterial, antifungal, antiviral, and antitumor activities [33]. Hydroperoxides and their alcohols have been obtained in excellent e.e. in the biocatalytic kinetic resolution of secondary hydroperoxides with horseradish and Coprinus peroxidase [34]. 

This catalytic asymmetric oxidation yielded J -methylphenylsulfoxide with a productivity of30g/l/day andane.e. >98% [35]. Chloroperoxidase is the most versatile peroxidase with better stability compared to other peroxidases, because spontaneous oxidation can be suppressed in the presence of ascorbic acid or dihydroxyfu-maric acid, and with better enantioselectivity because substrate access to the heme iron and ferryl oxygen favors stereoselective oxygen transfer [36]. Chloroperoxidase has been used for catalyzing the oxidation of cis-cydopropylmethanols with much higher enantioselectivity than trans-isomers [37]. 

Horseradish peroxidase (HPO) has been reported to be threefold more stable at 80°C in 5-10% [bmim+][BF ] as compared to phosphate buffer [28], Okrasa et al. [29] reported the asymmetric oxidation of phenyl methyl- and 2-naphthyl methyl sulphides to sulphoxides catalysed by peroxidase from Coprinus cinereus in [bmim ] [PP6-] with 10% water [29], Although the enantioselectivity (63-92% ee) and yields (<32%) were similar to those in water, the reaction workup was easier because ionic liquids and the extraction solvent did not form emulsions. 

Enzymes, in particular peroxidases, catalyze efficiently the enantioselective oxidation of alkyl aryl sulfides and also dialkyl sulfides, provided that the alkyl substituents are sterically differentiable by the enzyme. The peroxidases HRP, CPO, MP-11, and the mutants of HRP, e. g. F41L and F4IT, were successfully used as biocatalysts for the asymmetric sulfoxidation (Eq. 14). A selection of sulfides. 

Peroxidases have been used very frequently during the last ten years as biocatalysts in asymmetric synthesis. The transformation of a broad spectrum of substrates by these enzymes leads to valuable compounds for the asymmetric synthesis of natural products and biologically active molecules. Peroxidases catalyze regioselective hydroxylation of phenols and halogenation of olefins. Furthermore, they catalyze the epoxidation of olefins and the sulfoxidation of alkyl aryl sulfides in high enantioselectivities, as well as the asymmetric reduction of racemic hydroperoxides. The less selective oxidative coupHng of various phenols and aromatic amines by peroxidases provides a convenient access to dimeric, oligomeric and polymeric products for industrial applications. 

A similiar approach was performed by van de Velde (1999), using incorporation of vanadate into an acid phosphatase (phytase) to create a semi-synthetic peroxidase similar to the heme-dependent chloroperoxidase. The latter is a useful enzyme for the asymmetric epoxidation of olefins, but less stable due to oxidation of the porphyrin ring and difficult to express outside the native fungal host. The authors exploited the structural similarity of active sites from vanadate-dependent halo-peroxidases and acid phosphatases and have shown the useful application as an enantioselective catalyst for the synthesis of chiral sulfoxides (van de Velde, 1999). 

The rates of asymmetric sulfoxidation of thioanisole in nearly anhydrous (99.7%) isopropyl alcohol and methanol catalyzed by horseradish peroxidase (HRP) were determined to be tens to hundreds of times faster than in water under otherwise identical conditions (Dai, 2000). Similar effects were observed with other hemo-proteins. This dramatic activation is due to a much higher substrate solubility in organic solvents than in water and occurs even though the intrinsic reactivity of HRP in isopropyl alcohol and in methanol is hundreds of times lower than in water. In addition, the rates of spontaneous oxidation of the model prochiral substrate thioanisole in several organic solvents was observed to be some 100- to 1000-fold slower than in water. This renders peroxidase-catalyzed asymmetric sulf-oxidations synthetically attractive. 

Homocysteine decreases the bioavailability of nitrous oxide (NO) via a mechanism involving glutathione peroxidase (37). Tawakol et al. (38) reported that hyperhomocysteinemia is associated with impaired endothelium-dependent vasodilation in humans. Homocysteine impairs the NO synthase pathway both in cell culture (39) and in monkeys with hyperhomocysteinemia, by increasing the levels of asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor (40). Elevation of ADMA may mediate endothelial dysfunction during experimental hyperhomocysteinemia in humans (41). However, Jonasson et al. (42) did not find increased ADMA levels in patients with coronary heart disease and hyperhomocysteinemia, nor did vitamin supplementation have any effect on ADMA levels in spite of substantial plasma tHcy reduction,... 

Lutz, S., Steckhan, E. and Liese, A. (2004) First asymmetric electroenzymatic oxidation catalyzed by peroxidase. Electrochemistry Communications, 6, 583-587. 

Another reaction of heteroatom oxidation is that of S-oxidation, which leads to the synthesis of sulfoxides, a reaction not very common in the plant cell biochemical factory. Enantiomerically pure sulfoxides are important chiral synthons in asymmetric synthesis, in particular in enantio-selective carbon-carbon bond formation [77]. The sulfoxide functional group is involved in different biological activities, and optically pure sulfoxides are of great pharmaceutical interest [82]. However, plant peroxidases, such as horseradish peroxidase, catalyze the enantio-selective sulfoxidation of alkyl aryl sulfides ... 

Benzyl methylsulfide, thioanisol, and thiobenzamide were oxidized by chloroperoxidase, lactoperoxidase, and horseradish peroxidase to the respective sulfoxides. Whereas lactoperoxidase and horseradish peroxidase had low activities towards benzyl methylsulfide, thiobenzamide was efficiently oxidized by lactoperoxidase. Chloroperoxidase had high activity in halide-independent reactions towards all three substrates1251. This enzyme was also used for the asymmetric sulfoxidation of a series of cyclic sulfides. In all cases the (R)-sulfoxides were obtained. In the case of... 

Flavoprotein oxidases do not catalyze directly the oxidation of prochiral sulfides, but these biocatalysts have been used in combination with other oxidative enzymes to perform asymmetric sulfoxidations. Thus, flavoprotein oxidases are able to generate hydrogen peroxide in situ as a byproduct, which will be used as an oxidant by, for example, peroxidases or peroxygenases. This cascade methodology enhances the operational stability of peroxidases when compared with the one-pot addition of hydrogen peroxide. The direct addition of peroxides often leads to rapid inactivation of the employed enzyme [18]. 

Asymmetric alcohol oxidations Alcohol dehydrogenases, oxidases, and peroxidases... 

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