Biocatalytic Oxidation of Alcohols

Fig. 4.75 Biocatalytic oxidation of alcohol using acetone for cofactor recycling.

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

Advantageous use of homochiral cyclohexadiene-cis-l,2-diol, available by means of biocatalytic oxidation of chlorobenzene with toluene dioxygenase, has enabled the synthesis of all four enantiomerically pure C18-sphingosines (Nugent, 1998), which are known inhibitors of protein kinase C and important in cellular response mediation for tumor promoters and growth factors. The four requisite diastere-omers of azido alcohol precursors were accessed by regioselective opening of epoxides with either azide or halide ions. 

The alcohol dehydrogenases were already described in Chapter 3. These enzymes are cofactor dependent and in the active site hydrogen transfer takes place from NADH or NADPH. In the reverse way they can, however, be applied for the oxidation of alcohols in some cases (see below). Oxidases are very appealing for biocatalytic purposes, because they use oxygen as the only oxidant without the need for a cofactor. Oxidases usually have flavins (glucose oxidase, alcohol oxidase) or copper (examples galactose oxidase, laccase and tyrosinase) in the active site [18]. The mechanism for glucose oxidase (GOD) is denoted in... 

In short, we expect that the synthetic utility of both biocatalytic and biomimetic copper-based systems will be further improved in the future. This will provide economically viable catalytic methodologies for the green, atom efficient oxidations of alcohols employing molecular oxygen as the primary oxidant, and affording water as the sole byproduct. 

In short, we expect the interest in selective, environmentally benign oxidation of alcohols, using both chemo- and biocatalytic methodologies, to continue unabated in the future. 

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. 

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. 

Oxidation of secondary or primary alcohols by dehydrogenases is usually not performed biocatalytically. The reaction destroys a stereocentre, it is thermodynamically not favoured and product inhibition is a problem. It is attractive only in cases where it is necessary to discern between several hydroxy groups in a molecule. Microbial oxidation of D-glucitol to yield L-sorbose is the key step in production of vitamin C (Reichstein and Griissner, 1934). 

As VAO is able to perform an oxidative deamination of capsaicin-derived vanillyl amine, vanillin can be produced by the pathway described in the previous subsection. Van den Heuvel et al. [83] pointed out this biocatalytic route of synthesis in 2001 using penicillin G acylase to obtain vanillyl alcohol from natural capsaicin (Scheme 22.6). As the vanillin obtained can be labelled as natural. 

A composite biosensor was prepared by adding the desired amount of alcohol dehydrogenase (ADH) and NAD cofactor to a 50/50 % w/w MWCNT/Teflon composite. The electrocatalytic properties of MWCNT towards NADH and the biocatalytic properties of ADH are not impaired because of the presence of Teflon. A marked decrease in the overvoltage for the oxidation of the liberated NADH was shown. 

Sharma UK, Sharma N, Kumar R, Kumar R, Sinha AK (2009) Biocatalytic promiscuity of lipase in chemoselective oxidation of aryl alcohols/acetates a unique synergism of CAL-B and [hmim][Br] for the metal-free activation. Org Lett 11 4846-4848... 

Together with enantioselective hydrolysis/acylation reactions, enantioselective ketone reductions dominate biocatalytic reactions in the pharma industry [10], In addition, oxidases [11] have found synthetic applications, such as in enantioselective Baeyer-Villiger reactions [12] catalyzed by, for example, cyclohexanone monooxygenase (EC 1.14.13) or in the TEMPO-mediated oxidation of primary alcohols to aldehydes, catalyzed by laccases [13]. Hence, the class of oxidoreductases is receiving increased attention in the field of biocatalysis. Traditionally they have been perceived as difficult due to cofactor requirements etc, but recent examples with immobilization and cofactor regeneration seem to prove the opposite. 

Besides the multigram-scale production of different aliphatic carboxylic acids by biocatalytic alcohol oxidation, especially the enantioselective oxidation of racemic 2-phenyl-l-propanol to (S)-2-phenylpropanoic acid with Gluconobacter oxydans (Fig. 16.2-47) is another good example of acid production from alcohols12091. 

The enzyme vanillyl-alcohol oxidase (VAO, E.C. 1.1.3.38) was examined in detail with respect to mechanism, structural properties, and biotechnological applications by van Berkel and coworkers, giving an excellent example of how detailed biochemical studies provide a basis for preparative biocatalytic applications (for recent reviews see[1, 21). The homooctamer with a monomer mass of 65 kDa was isolated and purified from Penicillium simplicissimum. The catalytic mechanism of VAO-catalyzed oxidation of para-alkyl phenols was studied in detail[3-5 After initial hydride abstraction from the Ca atom, a binary complex of the intermediate para-quinone methide and reduced FAD reacts with molecular oxygen, regenerating the... 

Simultaneous biocatalytic oxidation and reduction was also reported for the resolution of secondary alcohols through combination of molecular oxygen and stereoselective reducing agent (alcohol dehydrogenase) with a cofactor-recycling... 

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