Olefin epoxidation cytochrome

As observed from reaction (6.19) and experimental data [41,120,121], ROOH satisfactorily replaces molecular oxygen and the reducer. When oxidized with hydroperoxides in the presence of iron porphyrin catalysts (cytochrome P-450 analogs), olefins mostly convert to allyl oxidation products, namely unsaturated alcohols and ketones, whereas the quantity of epoxides does not exceed 1% [122], According to current suggestions [121] such behavior of iron porphyrin catalysts is explained by olefin epoxidation with the cata-lyst-ROOH complex by the heterolytical mechanism according to the following equation ... 

Aromatic hydrocarbons are subject to cytochrome P-450-catalyzed hydroxylation in a process that is similar to olefin epoxidation. As discussed in Section IV. G, halogen migration observed during the hydroxylation of 4-ClPhe and similar substrates, led to the discovery of a general mechanism of oxidation that invokes arene oxide intermediates and the NIH shift. Arene oxides and their oxepin tautomers have not been isolated as products of metabolism of benzenoid compounds, but their presence has been inferred by the isolation of phenols, dihydrodiols and dihydrophenolic GSH conjugates derived therefrom262. 

Scheme 1 Typical reactions catalyzed by cytochromes P450 (a) hydroxylation of saturated hydrocarbons (b) heteroatom oxidation and dealkylation (c) olefin epoxidation (d) aromatic hydroxylation (e) desaturation (f) aldehyde deformylation.

Mechanism of olefin epoxidation catalyzed by cytochrome P450 enzymes 04CRV3947. 

Epoxidation of various olefins by cytochrome P-450 enzymes has been studied using rat liver microsomes [29,30] as well as using enzymes from microbial origin. For example, Ruettinger and Fulco [31] reported the epoxidation of fatty acids such as palmitoleic acid by a cytochrome P-450 from Bacillus megaterium. Their results indicate that both the epoxidation and the hydroxylation processes are catalyzed by the same NADPH-dependent monooxygenase. More recently, other researchers demonstrated that the cytochrome P-450cam from Pseudomonas putida, which is known to hydroxylate camphor at a non-activated carbon atom, is also responsible for stereoselective epoxidation of cis- -methylstyrene [32]. The (lS,2R)-epoxide enantiomer obtained showed an enantiomeric purity (ee) of 78%. This result fits the predictions based on a theoretical approach (Fig. 2). 

J. P. Collman, T. Kodadek, S. A. Raybuck, J. I. Brauman, L. M. Papazian, Mechanism of oxygen atom transfer from high valent iron porphyrins to olefins Implications to the biological epoxidation of olefins by cytochrome P-450, /. Am. Chem. Soc. 107 (1985) 4343. 

C. A. Martinez, J. D. Stewart, Cytochrome P450 s Potential catalysts for asymmetric olefin epoxidations, Curr. Org. Chem. 4 (2000) 263. 

D. N. Vaz, D. F. McGinnity, M. J. Coon, Epoxidation of olefins by cytochrome P450 Evidence from site-specific mutagenesis for hydroperoxo-iron as an electrophilic oxidant, Proc. Natl. Acad. Sci. USA 95 (1998) 3555. 

The first report of a simple iron porphyrin system that effected stereospecific olefin epoxidation and alkane hydroxylation was reported in 1979 (Scheme 1.7). This system introduced the use of iodosylbenzene as an oxygen-transfer agent to mimic the chemistry of cytochrome P450. ... 

Kamachi, T., Y. Shiota, T. Ohta, and K. Yoshizawa (2003). Does the hydroperoxo species of cytochrome P450 participate in olefin epoxidation with the main oxidant, compound I criticism from density functional theory calculations. Bull. Chem. Soc. Jpn. 6, 721-732. 

Vaz, A.D.N., D.F. McGinnity, P. Zarehbin-Irani, M.J. Coon, J.P. Salaun, D.R. Koop et al. (1997). Epoxidation of olefins by cytochrome P450 Possible role for hydroperoxo-iron as the direct oxidant. FASEBJ. 11, P207. 

HanzHk, R.P. and G.O. Shearer (1978). Secondary deuterium isotope effects on olefin epoxidation by cytochrome P450. Biochem. Pharmacol. 27, 1441-1444. 

Mansuy, D., J. Leclaire, M. Fontecave, and M. Momenteau (1984). Oxidation of monosubstituted olefins by cytochromes P450 and heme models Evidence for the formation of aldehydes in addition to epoxides and allylic alcohols. Biochem. Biophys. Res. Commun. 119, 319—325. 

Microperoxidase-11, MP-11, heme-undecapeptide, prepared by pepsin digestion of cytochrome c, retains the proximal His ligand and two thioether bonds between iron-protoporphyrin IX and two Cys residues. The peroxidase activities of MPs have been demonstrated in the oxidation of so-called peroxidase s substrates, phenolic compounds, in the presence of H2O2. MPs are unique and simple hemoprotein which are not restricted by consideration of the apoprotein structure. In this study, cytochrome P-450-hke reactivities of MP-11, sulfide oxidation, N-dealkylation, and olefin epoxidation, were... 

In conclusion, MP-11 catalyzed iV-demethylation, sulfide oxidation and olefin epoxidation in the cytochrome P-450-like manner. 

---