Alcohol biocatalytic

At first sight, it appears that it should be feasible to prepare such esters regioselectively using a similar biocatalytic approach to that employed for the 6- and 7-amino acylation of 6-APA and 7-ADCA shown above. Unfortunately, owing to the poor nucleophilicity of alcohols, biocatalytic esterification in aqueous media is far more challenging than amida-tion. Therefore, it was not until the pioneering work of Klibanov and co-workers, who first demonstrated the use of enzymes in neat organic solvents, that this option became viable (see Section 1.4). 

Several other biosensors have been developed usiag this oxygen-quenched fluorescence approach. Target species iaclude ethanol [64-17-5] hydrogen peroxide [7722-84-17, H2O2, lactate, and xanthine [69-89-6] C H4N402, usiag alcohol oxidase, catalase [9001-05-2] lactate oxidase, and xanthine oxidase, respectively. An additional technique for biocatalytic biosensors iavolves the firefly chemiluminescent reaction (17) ... 

The direct biocatalytic esterification of a chiral acid with a simple achiral alcohol in organic media is a reversible process and, in order to bias the equilibrium to the... 

The principal methods for the hydrolase-promoted synthesis of enantiomerically pure alcohols are depicted in Figure 6.44. Biocatalytic acylation and alcoholysis have been reviewed recently [116,117]. Lipases, esterases, and proteases catalyze these reactions, but CAL-B [118-120], CRL [121,122], and diverse lipase preparations from Pseudomonas species are common place. 

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

Deracemization via the biocatalytic stereoinversion is usually achieved by employing whole cells. In the case of secondary alcohols, it is believed that microbial stereoinversion occurs by an oxidation-reduction sequence... 

Scheme 5.13 Deracemization of secondary alcohols based on biocatalytic stereoinversion [26, 50b].

Kroutil W, Mang H, Edegger K, Faber K. 2004. Biocatalytic oxidation of primary and secondary alcohols. Adv Synth Catal 346 125-142. 

Prochiral aryl and dialkyl ketones are enantioselectively reduced to the corresponding alcohols using whole-cell bioconversions, or an Ir1 amino sulfide catalyst prepared in situ.695 Comparative studies show that the biocatalytic approach is the more suitable for enantioselective reduction of chloro-substituted ketones, whereas reduction of a,/ -unsaturated compounds is better achieved using the Ir1 catalyst. An important step in the total synthesis of brevetoxin B involves hydrogenation of an ester using [Ir(cod)(py) P(cy)3 ]PF6.696... 

Goldberg, K., Schroer, K., Luetz, S. and Liese, A. (2007) Biocatalytic ketone reduction - a powerful tool for the production of chiral alcohols -part I processes with isolated enzymes. Applied Microbiology and Biotechnology, 76, 237-248. 

Enantiometrically pure alcohols are important and valuable intermediates in the synthesis of pharmaceuticals and other fine chemicals. A variety of synthetic methods have been developed to obtain optically pure alcohols. Among these methods, a straightforward approach is the reduction of prochiral ketones to chiral alcohols. In this context, varieties of chiral metal complexes have been developed as catalysts in asymmetric ketone reductions [ 1-3]. However, in many cases, difficulties remain in the process operation, and in obtaining sufficient enantiomeric purity and productivity [2,3]. In addition, residual metal in the products originating from the metal catalyst presents another challenge because of the ever more stringent regulatory restrictions on the level of metals allowed in pharmaceutical products [4]. An alternative to the chemical asymmetric reduction processes is biocatalytic transformation, which offers... 

In a study aim to develop biocatalytic process for the synthesis of Kaneka alcohol, apotential intermediate for the synthesis of HMG-CoA reductase inhibitors, cell suspensions of Acine-tobacter sp. SC 13 874 was found to reduce diketo ethyl ester to give the desired syn-(AR,5S)-dihydroxy ester with an ee of 99% and a de of 63% (Figure 7.4). When the tert-butyl ester was used as the starting material, a mixture of mono- and di-hydroxy esters was obtained with the dihydroxy ester showing an ee of 87% and de of 51% for the desired, sy -(3/t,5,Sr)-dihydroxy ester [16]. Three different ketoreductases were purified from this strain. Reductase I only catalyzes the reduction of diketo ester to its monohydroxy products, whereas reductase II catalyzes the formation of dihydroxy products from monohydroxy substrates. A third reductase (III) catalyzes the reduction of diketo ester to, vv -(3/t,55)-dihydroxy ester. 

Kroutil, W., Mang, H., Edegger, K. and Faber, K. (2004) Recent advances in the biocatalytic reduction of ketones and oxidation of sec-alcohols. Current Opinion in Chemical Biology, 8 (2), 120-126. 

Edegger, K., Gruber, C.C., Poessl, T.M. et al. (2006) Biocatalytic deuterium- and hydrogen-transfer using overexpressed ADH- A enhanced stereoselectivity and 2/7-labeled chiral alcohols. Chemical Communications, (22), 2402-2404. 

Van den Heuvel, R.H.H., Laane, C. and van Berkel, W.J.H. (2001) Exploring the biocatalytic potential of vanillyl-alcohol oxidase by site-directed mutagenesis. Advanced Synthesis and Catalysis, 343 (6-7), 515-520. 

Voss, C.V., Gruber, C.C. and Kroutil, W. (2008) Deracemization of secondary alcohols through a concurrent tandem biocatalytic oxidation and reduction. Angewandte Chemie-International Edition, 47 (4), 741-745. 

US5846813 [48] desulfurization of DBT by Rhodococcus Sp. IGTS8. biodesulfurization of a fossil fuel by adding to the biocatalytic aqueous phase a nicotinamide adenosine dinucleotide and an additional amount of a group III alcohol dehydrogenase. Incubation and separation follows the mixing step. 

In this section, the enzymes, and associated substrates, used as biocatalysts in anodes are presented. For the development of biocatalytic anodes, there is a wide range of fuels available for use as substrates, such as alcohols, lactate, hydrogen, fructose, sucrose, all of which can be oxidized by biocatalysts. The fuel that is the most widely considered, however, in the context of an implantable biocatalytic fuel cell is glucose. We shall focus our attention on this fuel, but will mention briefly research on the use of some other fuels in biocatalytic anodes. 

O-Alkylation of 4-hydroxy-3-morpholino-l,2,5-thiadiazole 132 has been achieved with the chiral cyclic chloro-methyl sulfite 133 which subsequently suffers ring opening on treatment with simple alcohols <2001RCB436> or alkylamines <2002RJ0213> to afford the timolol analogues 134 with very little racemization (Scheme 20). This indicated an almost exclusive attack of the oxy anion on the exocyclic carbon atom and is a significant improvement on the previous oxirane method, which suffers from racemization. An alternative biocatalytic asymmetric synthesis of (A)- and (R)-timolol has also appeared <2004S1625>. 

Mateja Pogorevc, M. and Faber, K., Biocatalytic resolution of sterically hindered alcohols, carboxylic acids and esters containing fiiUy substituted chiral centers by hydrol)4ic enzymes. J. Mol. Catal. B, 2000,10, 357-376 and references cited therein. 

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