Chiral compounds enzymatic

Enzymatic KRs, as all resolutions, are limited to a maximum theoretical yield of 50%. Strategies to increase the yield are therefore of great importance. The opposite of a resolution, that is, the racemization of a chiral compound, can sometimes be highly desirable and applicable in enantioselective synthesis. By combining a... 

R0P032 is pra-prochiral, since two oxygen atoms must be substituted to produce a chiral compound. Chiral phosphates have been synthesized de novo by using stereospecific chemical and enzymatic reactions with isotopic and/or atomic substitutions. For example, a chiral phosphorothioate may be synthesized from a prochiral phosphate by replacing an oxygen atom with a sulfur atom. Similarly, what would otherwise be a pro-prochiral phosphate has been synthesized as a chiral product by replacing one oxygen atom with sulfur and another... 

Wada M, Yoshizumi A et al (2003) Production of a doubly chiral compound, (4R,6R)-4-hydroxy-2,2,6-trimethylcoclohexanone, by two-step enzymatic asymmetric reduction. Appl Environ Microbiol 69 933-937... 

Honda, K., Ishige, T., Kataoka, M., and Shimizu, S. 2006. Microbial and enzymatic process for the production of chiral compounds. In Patel, R. N. (Ed.), Biocatalysis in the Pharmaceutical and Biotechnology Industries (pp. 529-546). Boca Raton FL CRC Press. 

In conclusion, the combination of an enzymatic optical resolution and subsequent chemical transformations of epimerization or racemization of the asymmetric center of the unwanted antipodes have led to the successful development of processes for preparation of the two optically active pyrethroid insecticides. This work will provide a novel feature in the application of enzymes, especially lipases for the industrial production of chiral compounds. 

Keywords Chiral compounds, Dehydrogenases, Enzymatic reduction, Nicotinamide coenzymes, Regeneration of coenzymes... 

Presently, quite a lot of examples of enzymatic redox systems are known which include an efficient regenerating step and which are applied for large-scale manufacturing of important chiral compounds like fine chemicals or building blocks for pharmaceuticals in a very efficient way. 

Aryl-l,4-dihydropyridine-3,5-dicarboxylates are widely studied due to their use in the treatment of cardiovascular diseases. Most of these compounds are synthesized using the Hantzsch method (Section 4.2.3.4.2) but this is less suitable for the synthesis of unsymmetrical or chiral derivatives. Enzymatic desymmetrization of bis(ethoxycarbonyl-methyl)-l,4-dihydropyridine-3,5-dicarboxylates, using Candida antarctica lipase B, can generate enantiopure 1,4-dihy-dropyridines in reasonable to high yields with good enantiomeric selectivity <2000TA4559>. 

The distribution of metabolites obtained after incubation of pineapple slices with keto acids and keto esters, potential precursors of the corresponding hydroxy compounds, is summarized in Table II. The metabolization steps comprise esterification, reduction to hydroxy compounds, formation of acetoxy esters, and cyclization to the corresponding lactones. Metabolization rate and distribution of formed products strongly depend on the structures of the precursors. The detection of these metabolites proves the enzymatic capability of pineapple tissue to catalyze these conversions, an aspect which might be interesting for future use of pineapple tissue cultures in the production of chiral compounds. 

Gutman, A. L. Meyer, E. Kalerin, E. Polyak, F. Sterling, J., Enzymatic resolution of racemic amines in a continuous reactor in organic solvents. / Biotech. Bioeng. 1992,40,760 Gutman, A. L., Novel Methods in the Synthesis of Chiral Compounds. Spec. Chem. 1996, 16(7), 242. 

Allowing Nature to do part of the work is the central theme of Method 3. Numerous chiral molecules, isolated from natural sources and often available commercially, already contain much of the appropriate stereochemistry required in an enantioselective synthesis. These compounds are called the pool of chiral compounds. One reported synthesis of biotin (2), a molecule involved in enzymatic transfer of C02, used the methyl ester of the amino acid cysteine (1) as starting material.5 Note how 1 possesses a key stereocenter that later appears in biotin. 

CCCs may obtain chiral compounds by classical resolution, kinetic resolution using chemical or enzymatic metlrods, biocatalysis (enzyme systems, whole cells, or cell isolates), fermentation (from growing whole microorganisms), and stereoselective chemistry (e.g., asymmetric reduction, low-temperature reactions, use of chiral auxiliaries). CCCs may also be CCEs by capitalizing on a key raw material position and going downstream. Along with companies manufacturing chiral molecules primarily for other purposes, such as amino acid producers, these will be the key sources for the asymmetric center. 

Since 1980 several reviews have touched on the area of biohydrogenations7-17. The main incentive for choosing enzymatic methods for the hydrogenation of double bonds is to exploit the characteristic stereospecificity of enzymatic reactions. Thus, chiral products are obtained if the double bond of the substrate molecule is properly substituted. Such chiral products may be useful building blocks for the syntheses of chiral compounds. Further advantages of enzyme-catalyzed reactions are their high reaction specificity and rcgiospecificity as W ell as the mild reaction conditions under which they proceed. 

Both chiral compounds have been prepared by enantioselective reduction of ethyl-5-oxohexanoate 71 and 5-oxohexanenitrile 72 by Pichia methanolica SC 16116. Reaction yields of 80%-90% and more than 95% EEs were obtained for each chiral compound. In an alternate approach, the enzymatic resolution of racemic 5-hydroxy-hexane nitrile 73 by enzymatic succinylation was demonstrated using immobilized lipase PS-30 to obtain (S)-5-hydroxyhexanenitrile 69 in 35% yield (maximum yield is 50%). (S)-5-Acetoxy-hexanenitrile 74 was prepared by enantioselective enzymatic hydrolysis of racemic 5-acetoxyhexanenitrile 75 by Candida antarctica lipase. A reaction yield of 42% and an EE of more than 99% were obtained [96]. 

Chiral ligand 651 is obtained from the appropriate natural amino-acid phenylalanine, whereas the corresponding derivatives of valine or leucine proved to be slightly less effective [46], Axially prochiral, enantiotopic, biaryl-2,6-diols have been converted to the respective chiral compounds via enzymatic desymmetrization. Thus Pseudomonas cepacia lipase (PCL) catalysed the atropisomerically-selective hydrolysis of diacetate 654 to give monoacetate 655 in 67% yield and 96% e. e. [47], Scheme 24. 

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