Epoxidation enzymatic

In the following text, a brief overview of functionalization of various olefins is provided to give an outline of the current synthetic potential of this biooxygenation. 

Some of the major enzyme groups that facilitate this transformation are heme-containing MOs of the cytochrome P450 type [111], alkane hydroxylases, xylene monooxygenases, styrene monooxygenases [105], and haloperoxidases [112], 

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May SW, BJ Abbott (1973) Enzymatic epoxidation. II. Comparison between the epoxidation and hydroxyl-ation reactions catalyzed by the omega-hydroxylation system of Pseudomonas oleovorans. J Biol Chem 248 1725-1730. 

Chemo-enzymatic epoxidation of unsaturated fatty acids with aqueous H2O2 has been conducted with considerable success and here we have a remarkable situation that undesirable ring opening of the epoxide does not occur. Excellent activity and stability has been realized with Novozym 435, a Candida antartica lipase B immobilized on polyacryl. This enzyme is readily separable, can be used several times without loss of activity, and has a turnover of more than 2,00,000 moles of products per mole of catalyst (Bierman et al., 2000). 

Although many biochemical reactions take place in the bulk aqueous phase, there are several, catalyzed by hydroxynitrile lyases, where only the enzyme molecules close to the interface are involved in the reaction, unlike those enzyme molecules that remain idly suspended in the bulk aqueous phase [6, 50, 51]. This mechanism has no relation to the interfacial activation mechanism typical of lipases and phospholipases. Promoting biocatalysis in the interface may prove fruitful, particularly if substrates are dissolved in both aqueous phases, provided that interfacial stress is minimized. This approach was put into practice recently for the enzymatic epoxidation of styrene [52]. By binding the enzyme to the interface through conjugation of chloroperoxidase with polystyrene, a platform that protected the enzyme from interfacial stress and minimized product hydrolysis was obtained. It also allowed a significant increase in productivity, as compared to the use of free enzyme, and simultaneously allowed continuous feeding, which further enhanced productivity. 

Enzymatic epoxidation has proven to be the best method to achieve high enantio-selectivity348-350 [Eqs. (9.81) and (9.82)351 352]. 

The enantioselectivity of all three is very high. In the case of the antibody, however, the chemical epoxidation as a background reaction had to be taken into consideration for the experimental measured overall enantiomeric purity of 71% e.e. for the product. As the background reaction was about 30% of the total rate, the selectivity of the enzymatic epoxidation reaches a very high value with 98% e.e. 

The metabolism of naphthalene is similar to that of benzene, starting with an enzymatic epoxidation of the aromatic ring ... 

However, more recent mechanistic studies421,422 suggest that epoxidation involves oxygen transfer via a three-membered transition state. The proposed mechanism423 resembles that for the enzymatic epoxidation of olefins by iron-based mixed-function oxygenases discussed in Section V. 

Kim YH, An ES, Park SY et al (2007) Enzymatic epoxidation and polymerization of cardanol obtained from a renewable resource and curing of epoxide-containing polycardanol. J Mol Catal B Enzym 45 39-44... 

The next step is simple—the epoxidation of one of the terminal double bonds—but it leads to two of the most remarkable reactions in all of biological chemistry. Squalene is not chiral, but enzymatic epoxidation of one of the enantiotopic alkenes gives a single enantiomer of the epoxide with just one stereogenic centre. 

May, S. W., and Abbott, B. J. 1973. Enzymatic Epoxidation. 2. Comparison between Epoxidation and Hydroxylation Reactions Catalyzed by Omega-Hydroxylation System of Pseudomonas oleovorans. J. Biol. Chem., 248,1725-1730. 

Epoxide rings of alkene and arene compounds are hydrated to form trans-diols. The enzymes that catalyze the addition of a molecule of water to an epoxide ring to yield diols are called epoxide hydrolases (also known as epoxide hydrases). Epoxide hydrolase activity has been detected in numerous species of insects. Enzymatic epoxide hydration of certain cyclodiene insecticides and their analogs has been demonstrated in the housefly, blowfly (Calliphora erythrocephala), yellow mealworm (Tenebrio molitor), Madagascar cockroach (Gromphadorhina portentosa), southern army worm (Spodoptera eridania), and red flour beetle (Tribolium castaneum). Epoxide hydrolase is also important in the metabolism of juvenile... 

Recent studies have attempted to improve the efficiency of epoxidation under milder conditions that minimize the formation of byproducts. Chemo-enzymatic epoxidation uses the immobilized lipase from Candida antartica (Novozym 435) (56) to catalyze conversion of fatty acids to peracids with 60% hydrogen peroxide. The fatty acid is then self-epoxidized in an intermolecular reaction. The lipase is remarkably stable under the reaction conditions and can be recovered and reused 15 times without loss of activity. Competitive lipolysis of triacylglycerols is inhibited by small amounts of fatty acid, allowing the reaction to be carried out on intact oils (57). Rapeseed oil with 5% of rapeseed fatty acids was converted to epoxidized rapeseed oil in 91% yield with no hydroxy byproducts. Linseed oil was epoxidized in 80% yield. Methyl esters are also epoxidized without hydrolysis under these conditions. 

There are as yet no conclusions nor even a consensus hypothesis as to which types of chlorine substitution patterns govern ease of metabolism by enzymes. Some researchers favor the hypothesis that chlorine substitution at the 4,4 or combinations at the 3,5 3 5 positions of the biphenyl molecule block ease of enzymatic epoxidation of easily accessible vicinal carbons (14, 35). Other researchers suggest that 2,2 or 6,6 substitutions or some combination reduce coplanarlty of the biphenyl rings thereby causing a steric hlnderance to enzymatic activity or transfer across membranes (14, 36). Our data on Individual chloroblphenyla In biota does not yet encompass a wide enough range of chloroblphenyl structures to test these hypotheses which must be tested rigorously with Isotopically labeled chloroblphenyla In carefully controlled experiments In any event. 

M. A. Moreira, T. B. Bitencourt, M. D. G. Nascimento, Optimization of chemo-enzymatic epoxidation of cyclohexene mediated by lipases, Synth. Commun. 35 (2005) 2107. 

Warwel, S. and Rusch-Klaa, M., Chemo-enzymatic epoxidation of unsaturated carboxylic acids, J. Molec. Catal. B, 1, 29-35, 1995. 

However, the real breakthrough in the study of enzymatic epoxidations is due to Abbot and coworkers11031 and to May and coworkers[104), who established unequivo-... 

We will provide here three examples of recent applications concerned with the modeling of enzymatic epoxide transformation. Epoxides are versatile compounds and understanding their enzymatic transformation in detail is not only important from a fundamental enzymology point of view but also practically useful for biocatalytic applications. The three enzymes considered are LEH, the human sEH, and HheC. 

Scheme 2.15. Representative Enantioselective Enzymatic Epoxide Openings...

The MCS model introduces a simple, but nonetheless effective index M describing the probability of M-region activation as compared to detoxification pathways. A nonconcerted mechanism for the enzymatic epoxidation has been assumed on the basis of experimental [73] and theoretical [74] evidence. The ease of epoxidation is negatively correlated to Nm the smaller of the two Dewar reactivity numbers [36] in the M-region. 

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