Reductions enzymatic

Most asymmetric reductions effected enzymatically have been of ketones.t l The reactions have been conducted with whole cells (usually yeasts) as well as with isolated enzymes. In the latter case, of course, it is necessary to add at least an equivalent of the cofactor NADH or NADPH (nicotinamide adenine dinucleotide) as the actual reductant. 

The dihydroxyacetone reductase of Mucor javanicus is NADPH-dependent, and accepts a wide variety of simple acyclic ketones. For 2-alkanones, hydride attack occurs largely from the Si face with high selectivity to give the (/ )-product. However, butan-2-one was reduced to racemic butan-2-ol, indicating that methyl and ethyl are not differentiated by the enzyme. 

The opposite enantiomer predominates in the reduction of simple ketones by baker s yeast (Saccharomyces cerevisiae)  

The synthetic value of S. cerevisiae is increased by the fact that its oxidoreductase(s) will accept haloketones as substrates, reducing them with reasonable enantioselectivity to the (R) enantiomer. (Note that the stereochemical outcome is the same, despite the apparent inversion due to the CIP rules.) 

The most widely used substrates in reduction by yeast have been P-ketoesters and P-ketoacids, since the products are valuable chiral building blocks. The enantiomer obtained and the e.e. are critically dependent on the substituents. 

---

The product of this reaction 3 hydroxy 3 methylglutaryl coenzyme A (HMG CoA) has the carbon skeleton of mevalonic acid and is converted to it by enzymatic reduction... 

Reaction of an achiral reagent with a molecule exhibiting enantiotopic faces will produce equal quantities of enantiomers, and a racemic mixture will result. The achiral reagent sodium borodeuteride, for example, will produce racemic l-deM/eno-ethanol. Chiral reagent can discriminate between the prochiral faces, and the reaction will be enantioselective. Enzymatic reduction of acetaldehyde- -[Pg.106]

S Enzymatic Reduction Reaction Substrate Suitable microbe (a)... 

Dynamic kinetic resolution of racemic ketones proceeds through asymmetric reduction when the substrate does racemize and the product does not under the applied experimental conditions. Dynamic kinetic resolution of a-alkyl P-keto ester has been performed through enzymatic reduction. One isomer, out of the four possible products for the unselective reduction (Figure 8.38), can be selectively synthesized using biocatalyst, and by changing the biocatalyst or conditions, all of the isomers can be selectively synthesized [29]. 

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

Hoffmann DK, Ruedenberg K, Verkade JG (1977) Molecuar Orbital Bonding Concepts in Polyatomic Molecules - A Novel Pictorial Approach. 33 57-96 Hogenkamp HPC, Sando GN (1974) The Enzymatic Reduction of Ribonucleotides. 20 23-58 Housecroft CE (1997) Clusters with Interstitial Atoms from the p-Block How Do Wade s Rules Handle Them 87 137-156 Huber R, see Romao MJ (1998) 90 69-96... 

The value of critical concentration depends strongly on the pectin being used. Figure 2 gives the viscosity curves of two different pectins at the same concentration of 2.5 % w/w. The different production parameters, that have been used for these pectins, have strongly influenced their flow behaviour. The enzymatic reduction of the molecular weight down to... 

Dorner E, M Boll (2002) Properties of 2-oxoglutarate ferredoxin oxidoreductase from Thauera aromatica and its role in enzymatic reduction of the aromatic ring. J Bacterial 184 3975-3983. 

Koch J, G Fuchs (1992) Enzymatic reduction of benzoyl-CoA to alicyclic compounds, a key reaction in anaerobic aromatic metabolism. Eur J Biochem 205 195-202. 

As mentioned above, Met(0) must be converted to Met before it can be incorporated into proteins. There are a wide variety of organisms that have been shown to be capable of enzymatically reducing Met(O) residues. The enzymatic reduction of free Met(O) to Met has been observed in yeast , E. cofi - , Pseudomonas , plants and animal tissues . The enzyme from E. coli has been purified about 1100-fold using a newly developed very sensitive assay . The assay involves first the conversion of [ S]Met(0) to [ S]Met by the Met(O) reductase followed by the measurement of [ S]Met-tRNA after enzymatic acylation of tRNA. Since Met(O) is not a substrate for the acylation reaction , the amount of [ S]Met-tRNA formed is proportional to the amount of [ S]Met(0) converted to [ S]Met. The assay is sensitive to Met levels of less than 1 pmol. 

---