Kinetic-enzymatic oxidation

Figure 4.10 Factor effects in the kinetic-enzymatic oxidation of p-phenylenediamine (PPD) by the enzyme ceruloplasmin.

The classical kinetic resolution of racemic substrate precursors allows only access to a theoretical 50% yield of the chiral ladone product, while the antipodal starting material remains unchanged in enantiomerically pure form. The regioseledivity for the enzymatic oxidation correlates to the chemical readion with preferred and exclusive migration of the more nucleophilic center (usually the higher substituted a-carbon). The majority of cydoketone converting BVMOs (in particular CHMOAdneto)... 

G. P. Akulov, N. A. Korsakova, and B. K. Kudelin, Use of kinetic isotope effects in enzymatic oxidation of D-[6-3H]galactose for increasing its molar activity, J. Labelled Comp. Radiopharm., 27 (1989) 803-810. 

In the oxidative polymerization of phenols catalyzed by Cu complexes, the substrate coordinates to the Cu(II) complex and is then activated. The activated phenol couples in the next step. The Cu complex acts effectively as a catalyst at concentrations of 0.2-2 mol% compared to the substrate. The oxidation proceeds rapidly at room temperature under an air atmosphere to give poly(phenylene ether) in a quantitative yield. The polymerization follows Michaelis-Menten-type kinetics [55]. Enzymatic oxidation of phenols is an important pathway in the biosynthesis of lignin in plants [56] catalyzed by a metalloenzyme. 

Kinetic resolution with racemisation Enzymes versus whole organisms Desymmetrisation with lipases Immobilised enzymes in desymmetrisation Polymer-supported reagents and enzymes Effects of amines on lipases and esterases Other acylating enzymes Enzymatic Oxidation... 

Metal-peroxo intermediates of different structures were often implicated in the catalytic cycles of oxidative enzymes (see Figures 4.32 1.35 for representative examples). In most cases, however, these peroxo complexes are incompetent oxidants for native substrates. Instead, they undergo further reactions (usually, 0-0 bond cleavage that generates high-valent metal-oxo species) yielding more reactive, kinetically competent oxidants. Nevertheless, some peroxides can react with substrates in both enzymatic and synthetic systems. 

Kinetic-based methods employing catalytic (especially enzymatic) reactions are inherently more selective than many comparable chemical equilibrium methods. For example, of the approximately sixty oxidizable sugars and their derivatives, only two OS-D-glucose and 2-deoxy-D-glucose) are enzymatically oxidized by glucose oxidase at a significant rate. The oxidation of all others, including the isomeric... 

These optimized conditions were used to perform the preparative transformation on a 0.5 g scale, demonstrating the applicability of the BBE-catalyzed kinetic resolution of different benzylisoquinoline and berbine alkaloids. An impressive example employing the described enzymatic oxidative intramolecular C—C bond formation by the BBE can be found in the first asymmetric total synthesis of the natural product (S)-scoulerine, a sedative and muscle-relaxing agent, which was obtained in 7.4% yield over nine linear steps [166]. 

In studies with chloroperoxidase (CPX), a peroxidative enzyme that is amazingly similar in certain properties to cytochrome P-450, we found the nitrosoarene metabolite to be the terminal product of arylamine oxidation (Fig. 6) (23, 31). CPX has been used to prepare nitrosoarene chemicals on a micro scale (17) because few chemical techniques are available for the direct conversion of arylamines to nitrosoarene compounds (28). It is probable that this enzymatic oxidation produces an intermediary hydroxylamine compound which, under the reaction conditions, is rapidly converted to the nitroso level. An apparent kinetic block in the oxidation of nitrosoarene to nitroaromatic compounds allows for the fairly selective production of the former by mild oxidants, particularly for those arylamines with electron-withdrawing substituents. 

A more detailed study of the biological oxidation of sulphoxides to sulphones has been reported165. In this study cytochrome P-450 was obtained in a purified form from rabbit cells and was found to promote the oxidation of a series of sulphoxides to sulphones by NADPH and oxygen (equation 56). Kinetic measurements showed that the process proceeds by a one-electron transfer to the activated enzymatic intermediate [an oxenoid represented by (FeO)3+] according to equation (57). 

Enantiomers, preferential crystallization of 59 Endo selectivity 798 Ene reactions 808, 809 Enones, synthesis of 732 Enthalpies of formation 102, 103 Enynes, synthesis of 956 Enzymatic kinetic resolution 829 Epimerization 399 Episulphides, oxidation of 237 Episulphones 650, 775 Episulphoxides, photolysis of 742 a,/J-Epoxysulphones reactions of 811, 812 rearrangement of 685 synthesis of 612 / ,y-Epoxysulphones 781 y,<5-Epoxysulphones 627, 628 Epoxysulphoxides reactions of 613 rearrangement of 744 synthesis of 327, 612 Erythronolides 831... 

Carbonaceous Deoxygenation. In this process microorganisms, principally bacteria, enzymatically mediate oxidation of simple and complex organic substances according to first order decay kinetics. 

CK catalyzes the reversible phosphorylation of creatine in the presence of ATP and magnesium. When creatine phosphate is the substrate, the resulting creatine can be measured as the ninhydrin fluorescent compound, as in the continuous flow Auto Analyzer method. Kinetic methods based on coupled enzymatic reactions are also popular. Tanzer and Gilvarg (40) developed a kinetic method using the two exogenous enzymes pyruvate kinase and lactate dehydrogenase to measure the CK rate by following the oxidation of NADH. In this procedure the main reaction is run in a less favorable direction. 

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