Oxidases, 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. ... 

Figure 18 Glucose oxidase-mediated asymmetric oxidation of sulfide in IL...

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... 

Improved efficiency in the synthesis of 24 was ultimately achieved via an enzymatic desymmetrization approach (Scheme 7). In the key step of this route, an asymmetric oxidation of achiral amine 41 promoted by monoamine oxidase (MAON) under an oxygen atmosphere afforded intermediate 42. In this streamlined process, sodium bisulfite was included in the enzymatic oxidation mixture to effect direct conversion to sulfonate 44. Treatment of 44 with sodium cyanide provided the trans-nitrile 43 as a single diastereomer in approximately 90% yield from pyrrolidine 41. As in the second-generation synthesis, the nitrile is hydrolyzed to the methyl ester under Pinner conditions (HCI, methanol). In the manufacturing process, the product was converted to its free base using NaOH, then crystallized as the HCI salt from i-propanol and methyl t-... 

Hewgley, B., Stahl S. and Kozlowski, M. (2008). Mechanistic Study of Asymmetric Oxidative Biaryl Coupling evidence for Self-Processing of the Copper Catalyst to Achieve Control of Oxidase vs Oxygenase Activity, J. Am. Chem. Soc., 130, pp. 12232-12233. 

Bovine heart cytochrome c oxidase is in a dimer state in the asymmetric unit of the crystal as shown in Fig. 7 (see color insert) (Tsukihara et al., 1996). Thirteen different subunits were identified in each monomer in the X-ray structure of the fully oxidized enzyme at 2.8-A resolution. The top view from the intermembrane side indicates a fairly strong interaction between the two monomers. The middle portion of the side view is readily identified as the transmembrane region by the large cluster of a-helices. This part was composed mainly of 28 a-helices as had been predicted by the amino acid sequences. The Ga backbone traces show that most of the a-helices are not arranged stricdy perpendicularly to the membrane surfaces, in contrast to the prediction by the amino acid sequences. Thus, most of a-helices in the X-ray structure are longer than those predicted by the amino acid sequences. The three largest subunits, subunits I, II, and III, form a core portion and the other 10 nuclear-encoded subunits surround the core as shown in Figs. 7C and 7D. In the X-ray structure at 2.8-A resolution, 3560 of 3606 amino acid residues were identified in the asymmetric unit composed of a dimer. Only 23 of 1803 amino acid residues per monomer were not detectable in the electron density map. Most of the undetectable residues are in the N- and C-terminals, which are exposed to the bulk water phase. 

Oxidation of Meso Diols. Asymmetric induction of meso and prochiral diols by lipases is very successful in the field of organic synthesis. Also it is well known that selective oxidation of prochiral or meso diols by HLADH provides oxidized products with a significant degree of enantioselectivity. However, it has not been reported that alcohol oxidases were applied to such types of oxidation. The microbial oxidation of meso diols by Candida boidinii SA051 was carried out and gave optically active hydroxy ketones (Figure 8). 

There are several examples of d to l inversion of amino acids in the literature. D-Phenylalanine may have therapeutic properties in endogenous depression and is converted to L-phenylalanine in humans [145]. o-Leucine is inverted to the L-enantiomer in rats. When o-enantiomer is administered, about 30% of the enantiomer is converted to the L-enantiomer with a measurable inversion from l to o-enantiomer. As indicated in Fig. 13, D-leucine is inverted to the L-enantiomer by two steps. It is first oxidized to a-ketoisocarproate (KIC) by o-amino acid oxidase. This a-keto acid is then asymmetrically reaminated by transaminase to form L-leucine. In addition, KIC may be decarboxylated by branched-chain a-keto acid dehydrogenase, resulting in an irreversible loss of leucine (Fig. 13) [146]. D-Valine undergoes a similar two-step inversion process, and this can be antagonized by other amino acids such as o-leucine. The primary factor appears to be interference with the deamination process [147]. 

The asymmetric transfer hydrogenation of ketones is an effective way to prepare enan-tiopure alcohols." " We were attracted to this reaction as we anticipated that one could exploit the reversibility of the reaction to perform either for the enantioselective reduction or for the kinetic resolution of racemic alcohols via oxidation. This behaviour is reminiscent of alcohol dehydrogenases which can operate either as oxidases or reductases. ... 

Asymmetric induction by polymer-immobilized complexes is an important reaction in oxidation processes (this has already been demonstrated for the hydrogenation transformations described in Section 12.2.9). There are three different methods of synthesis of optically active compounds from optically inactive racemic mixtures spontaneous, biochemical and chemical. The chemical method is the most common. Immobilized metal complexes are the best models of asymmetric induction by enzymes. They produce large quantities of enantiomeric products from small quantities of chiral compounds. (Ascorbate oxidase is a copper-containing enzyme catalyzing aerobic oxidation of vitamin C. Its... 

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]. 

CiP was also used in the synthesis of heteroaryl methyl sulfoxides combined with glucose oxidase as a hydrogen peroxide source, as shown in Scheme 6.1 [21]. Optically active heteroaryl alkyl sulfoxides are interesting compounds in organic chemistry, as they present a chelating center that can be used in asymmetric s mthe-sis. Moderate to good results were achieved depending on the substrate structure. The best results were obtained for the oxidation of sulfides with electron-rich heterocycles. 

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

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