Oxidation flavin-catalyzed

Silverman s studies on mechanism based MAO inactivation have provided overwhelming support for the role of electron transfer in the MAO catalyzed dealkylation of amines. It must be mentioned however that spectroscopic attempts for detecting the radical ion intermediates have hitherto been unsuccessful. Yasanobu and coworkers could not find EPR spectral evidence for radical intermediates in MAO-catalyzed oxidation of benzylamine [205]. Miller et al. failed to observe the flavin semiquinone or an amine-flavin adduct in rapid-scan-stopped flow spectroscopy [206]. The only time-dependent absorption change observed in this study was the bleaching of the oxidized flavin. Furthermore, no influence of a magnetic field up to 6500 G was observed on the rate of MAO B reduction. The reaction rates of systems with kinetically significant radical pair intermediates are known to be altered... 

In the MAO-catalyzed reaction, intermediate structure 10 is converted directly to structure 12. As shown in figure 2, the electron acceptor for the cytochrome P450-catalyzed reaction is the perferryl 0X0 species (Fe O), while the electron acceptor for the MAO-catalyzed reaction is the oxidized flavin moiety (FAD). 

In the first step of the flavin-catalyzed oxidation of an amino acid to an imino acid, a basic side chain at the active site of the enzyme removes a proton from the a-carbon of the amino acid. The carbanion that is formed attacks the N-5 position of the flavin ring. Collapse of the resulting tetrahedral intermediate gives the oxidized amino acid (an imino acid) and the reduced coenzyme (FADH2). 

Murahashi, S.-L, Oda, T., Masui, Y. (1989). Flavin-catalyzed oxidation of amines and sulfur compounds with hydrogen peroxide, J. Am. Chem. Soc., Ill 5002. 

Figure 11.9 Flavoenzyme catalyzed electron transfer and oxidation/oxygenation reactions The extensive conjugation of the isoaUoxazine ring system results in the yellow chromophore ( ax = 450 nm) in the oxidized flavin. Flavin semiquinones are stable radicals, because the unpaired electron is highly delocalized through the conjugated isoaUoxazine structure. The neutral semiquinone is blue = 570 nm) and the flavosemiquinone anion is red (A ax = 480 nm). The...

For sulfoxides/sulfides, oxidation is catalyzed by cytochrome P-450 and flavin monooxygenases, whereas the reductive metabolism is catalyzed by aldehyde oxidase and/or thiotedocin-linked enzymes. The fiver as well as the gut and bacterial flora are potential sites for the formation of sulfide metabolites. 

The catalytic mechanism of the asymmetric reduction of alkenes catalyzed by ene-reductases has been studied in great detail [977] and it has been shown that a hydride (derived from a reduced flavin cofactor) is stereoselectively transferred onto Cp, while a Tyr-residue adds a proton (which is ultimately derived from the solvent) onto Cot from the opposite side (Scheme 2.134). As a consequence of the stereochemistry of this mechanism, the overall addition of [H2] proceeds in a trans-fashion with absolute stereospecificity [978]. This reaction is generally denoted as the oxidative half reaction . The catalytic cycle is completed by the so-called reductive half reaction via reduction of the oxidized flavin cofactor at the expense of NAD(P)H, which is ultimately derived from an external H-source via another... 

All mechanistic studies on enzymatic Baeyer-Villiger reactions support the hypothesis that conventional and enzymatic reactions are closely related [1063, 1204]. The oxidized flavin cofactor (FAD-4a-OOH, see Scheme 2.147) plays the role of a nucleophile similar to the peracid. The strength of enzyme-catalyzed Baeyer-Villiger reactions resides in the recognition of chirality [1205-1207], which has been accomplished by conventional means only recently, albeit in reactions exhibiting moderate selectivities [1208]. 

The mechanism of the flavin-catalyzed oxidation of sulfides by hydrogen peroxide is shown in Scheme 8.3. 

Murahashi has reported on an interesting flavin-catalyzed aerobic oxidation of sulfides to sulfoxides (Scheme 8.4) [59]. Flavin hydroperoxides can be generated from reaction of the lowest reduced form of the flavin (16) and molecular oxygen. These hydroperoxides (18) have been studied in stoichiometric oxidation of sulfides to sulfoxides by Bruice [42]. 

Dimethylglycine is formed by endogenous demethylation of betaine, a choline metabolite, with concomitant methylation of homocysteine to methionine. DMG is then converted to sarcosine by oxidative demethylation catalyzed by DMG-dehydrogenase, a flavin-containing enzyme requiring folate as a cofactor. Increased excretion of DMG has been observed in individuals with folate deficiency or receiving large doses of betaine as a... 

The flavin-catalyzed sulfoxidation was recently extended to aUylic and vinylic sulfides. It was found that the oxidation of allylic sulfides having electron-rich double bonds proceed with an exceptional selectivity for sulfoxidation (Table 7.5) [37]. Sul-... 

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