Enzyme-catalyzed asymmetric oxidation

Chapters 2 through 6 introduced many asymmetric organic reactions catalyzed by small molecules, such as C-C bond formation, reduction, and oxidation reactions. Chapter 7 provided further examples of how asymmetric reactions are used in organic synthesis. This chapter starts with a general introduction to enzyme-catalyzed asymmetric organic reactions. 

Optically active epoxides are important building blocks in asymmetric synthesis of natural products and biologically active compounds. Therefore, enantio-selective epoxidation of olefins has been a subject of intensive research in the last years. The Sharpless [56] and Jacobsen [129] epoxidations are, to date, the most efficient metal-catalyzed asymmetric oxidation of olefins with broad synthetic scope. Oxidative enzymes have also been successfully utilized for the synthesis of optically active epoxides. Among the peroxidases, only CPO accepts a broad spectrum of olefinic substrates for enantioselective epoxidation (Eq. 6), as shown in Table 8. 

Enantiomerically pure sulfoxides play an important role in asymmetric synthesis either as chiral building blocks or stereodirecting groups [156]. In the last years, metal- and enzyme-catalyzed asymmetric sulfoxidations have been developed for the preparation of optically active sulfoxides. Among the metal-catalyzed processes, the Kagan sulfoxidation [157] is the most efficient, in which the sulfide is enantioselectively oxidized by Ti(OzPr)4/tBuOOH in the presence of tartrate as chirality source. However, only alkyl aryl sulfides may be oxidized by this system in high enantiomeric excesses, and poor enantioselectivities were observed for dialkyl sulfides. 

Two approaches were studied to obtain (R)-l,3-BDO. The first was based on an enzyme-catalyzed asymmetric reduction of 4-hydroxy-2-butanone, and the second was based on enantioselective oxidation of the undesirable (S)-l,3-BDO in the racemate. As a result of screening for yeasts, fungi, and bacteria, the enzymatic resolution of racemic 1,3-BDO by Candida parapsilosis IFO 1396, which showed differential rates of oxidation for two enantiomers, was found to be the most practical process to produce (R)-l,3-BDO with high enantiomeric excess and yield. 

In contrast to [3-carotene, a-carotene, or P-cryptoxanthin, lycopene is not a provitamin A carotenoid the absence of the P-ionone rings at the two ends of the molecule prevents its acceptance as a substrate by the 15,15 central cleavage enzyme to generate retinal. A mammalian enzyme that catalyzes asymmetrical oxidative cleavage of P-carotene at the 9, 10 position has recently been identified this cleaved lycopene to form apolycopenales... 

Asymmetric induction by polymer-immobilized complexes is an important reaction in oxidation processes (this has already been demonstrated for the hydrogenation transformations described in Section 12.2.9). There are three different methods of synthesis of optically active compounds from optically inactive racemic mixtures spontaneous, biochemical and chemical. The chemical method is the most common. Immobilized metal complexes are the best models of asymmetric induction by enzymes. They produce large quantities of enantiomeric products from small quantities of chiral compounds. (Ascorbate oxidase is a copper-containing enzyme catalyzing aerobic oxidation of vitamin C. Its... 

The biomimetic approach to total synthesis draws inspiration from the enzyme-catalyzed conversion of squalene oxide (2) to lanosterol (3) (through polyolefinic cyclization and subsequent rearrangement), a biosynthetic precursor of cholesterol, and the related conversion of squalene oxide (2) to the plant triterpenoid dammaradienol (4) (see Scheme la).3 The dramatic productivity of these enzyme-mediated transformations is obvious in one impressive step, squalene oxide (2), a molecule harboring only a single asymmetric carbon atom, is converted into a stereochemically complex polycyclic framework in a manner that is stereospecific. In both cases, four carbocyclic rings are created at the expense of a single oxirane ring. 

Kiefer, C. et al.. Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A, J. Biol. Chem., 276, 14110, 2001. 

Kiefer C, Hessei S, Lampert JM, Vogt K, Lederer MO, Breithaupt DE, and von Lintig J (2001) Identification and characterization of a mammaiian enzyme catalyzing the asymmetric oxidative cieavage of provitamin A. Journal of Biological Chemistry 276, 14110-16. 

The award of the Nobel Prize in Chemistry in 2001 to William R. Knowles and Ryoji Noyori for their work on metal-catalyzed enantioselective hydrogenation reactions and to K. Barry Sharpless for his work on catalyzed enantioselective oxidation reactions was a landmark in chiral catalysis studies. Enzymes and biocatalysts have also played a pivotal role as asymmetric catalysts [16]. 

Racemic mixtures of secondary alcohols can be resolved completely by enantiospe-cific enzyme-catalyzed oxidation resulting in one enantiomer of the alcohol and the ketone followed by asymmetric enzyme-catalyzed reduction of the ketone (Fig. 16.2-51). For oxidation and reduction, two separate microorganisms1217-2191 or two different enzymes in a single microorganism1220-2221 may be used. 

FDH catalyzes the oxidation of formate to carbon dioxide, concomitant with the reduction of NAD+ to NADH (Fig. 16.6-4). Because of the favorable thermodynamic equilibrium of the reaction and the volatility of the reaction product, the enzyme is commonly applied for in situ regeneration of NADH during asymmetric synthesis of chiral compounds1131. 

Kiefer, C., S. Hessel, J. M. Lampert, et al. 2001. Identification and Characterization of a Mammalian Enzyme Catalyzing the Asymmetric Oxidative Cleavage of Provitamin A. JBiol Chem 276, no 17 14110-16. 

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