Resolution by enzymes

DYNAMIC KINETIC RESOLUTIONS BY ENZYME-METAL COMBINATIONS... 

Quartey, E.G.K., Hustad, J.A., Faber, K. and Anthonsen, T. (1996) Selectivity enhancement of PPL-catalysed resolution by enzyme-fractionation and mediumengineering Synthesis of both enantiomers of tetrahydropyran-2-methanol. Enzyme. Microb. Technol., 19, 361-366. 

Dynamic Kinetic Resolutions by Enzymes Coupled with Metal Catalysts... 

By far the commonest reaction used in kinetic resolution by enzymes is ester formation or hydrolysis. Normally one enantiomer of the ester is formed or hydrolysed leaving the other untouched so one has the easy job of separating an ester from either an acid or an alcohol. There are broadly two kinds of enzymes that do this job. Lipases hydrolyse esters of chiral alcohols with achiral acids such as 119 while esterases hydrolyse esters of chiral acids and achiral alcohols such as 122. Be warned this definition is by no mans hard and fast If the unreacted component (120 or 123) is wanted, the reaction is run to just over 50% completion, to ensure complete destruction of the unwanted enantiomer, while if the reacted component (121 or 124) is wanted it is best to stop short of 50% completion so that little of the unwanted enantiomer reacts. 

Kinetic resolution of racemic allylic acetates has been accomplished via asymmetric dihydroxylation (p. 1051), and 2-oxoimidazolidine-4-carboxy-lates have been developed as new chiral auxiliaries for the kinetic resolution of amines. Reactions catalyzed by enzymes can be utilized for this kind of resolution. ... 

Martin-Matute, B. and Baeckvall, J.-E. (2007) Dynamic kinetic resolution catalyzed by enzymes and metals. Current Opinion in Chemical Biology, 11 (2), 226-232. 

Other examples of efficient enzymatic resolutions by reaction at a remote position from stereocentres have been reported, such as the lipase-catalysed resolution of a synthetic intermediate of escitalopram." This property of enzymes has also been effectively used to resolve sterically hindered compounds by the introduction of a tether so that the enzyme-catalysed reaction can be performed at an artificially created, but less hindered, remote location. An example is the resolution of tertiary alcohols by the introduction of a glyoxylate ester. 

Allan, G., Camell, A.J., Escudero Hernandez, M.L. and Pettman, A., Desymmetrisation of 4,4-disubstituted cyclohexanones by enzyme-catalysed resolution of their enol acetates. J. Chem. Soc. Perkin Trans. 1, 2000, 3382. 

As shown in Table 12,H202 and fBuOOH have been used frequently as oxygen donors in peroxidase-catalyzed sulfoxidations. Other achiral oxidants, e.g. iodo-sobenzene and peracids, are not accepted by enzymes and, therefore, only racemic sulfoxides were found (c.f. entries 34-36). Interestingly, racemic hydroperoxides oxidize sulfides to sulfoxides enantioselectively under CPO catalysis [68]. In this reaction, not only the sulfoxides but also the hydroperoxide and the corresponding alcohol were produced in optically active form by enzyme-catalyzed kinetic resolution (cf. Eq. 3 and Table 3 in Sect. 3.1). 

Reactions catalyzed by enzymes or enzyme systems exhibit far greater specificities than more conventional organic reactions. Among these specificities which enzymatic reactions possess, stereospecificity is one of the most excellent. To overcome the disadvantage of a conventional synthetic process, i.e., the troublesome resolution of a racemic mixture, microbial transformation with enzymes possessing stereospecificities has been appHed to the asymmetric synthesis of optically active substances [1-10]. C3- and C4-synthetic units (synthons, building blocks), such as epichlorohydrin (EP), 2,3-dichloro-l-propanol (2,3-DCP), glycidol (GLD), 3-chloro-l,2-propanediol (3-CPD), 4-chloro-... 

Janssen, A. J. M. Klunder, A. J. H. Zwanenburg, B. Resolution of secondary alcohols by enzyme-catalyzed transesterification in alkyl carboxylates as the solvent. Tetrahedron 1991, 47, 7645-7662. 

Acid dye method for the analysis of thiamin, 18A, 73 electrophoretic separation and fluorometric determination of thiamin and its phosphate esters, 18A, 91 catalytic polarography in the study of the reactions of thiamin and thiamin derivatives, 18A, 93 preparation of thiamin derivatives and analogs, 18A, 141 preparation of the mono- and pyrophosphate esters of 2-methyl-4-amino-5-hydroxymethylpyrimidine for thiamin biosynthesis, 18A, 162 formation of the pyrophosphate ester of 2-methyl-4-amino-5-hydroxymethylpyrimidine by enzymes from brewers yeast in thiamin biosynthesis, 18A, 203 resolution, reconstitution, and other methods for the study of binding of thiamin pyrophos-... 

Preparation of Enantiomerically Pure (2R)- and (2S)-Ethyl-2-Fluorohexanoate by Enzyme-Catalyzed Kinetic Resolution... 

Kinetic resolutions by means of the selective formation or hydrolysis of an ester group in enzyme-catalyzed reactions proved to be a successful strategy in the enantioseparation of 1,3-oxazine derivatives. Hydrolysis of the racemic laurate ester 275 in the presence of lipase QL resulted in formation of the enantiomerically pure alcohol derivative 276 besides the (23, 3R)-enantiomer of the unreacted ester 275 (Equation 25) <1996TA1241 >. The porcine pancreatic lipase-catalyzed acylation of 3-(tu-hydroxyalkyl)-4-substituted-3,4-dihydro-2/7-l,3-oxazines with vinyl acetate in tetrahydrofuran (THF) took place in an enantioselective fashion, despite the considerable distance of the acylated hydroxy group and the asymmetric center of the molecule <2001PAC167, 2003IJB1958>. 

This is one process in which the initial research was carried out in an academic lab. Whitesides and co-workers showed that resolution by stereoselective enzyme hydrolysis of racemic (+/-) glycidyl butanoate was possible (Figure 4.16). 

A very important process is the kinetic resolution of acetylated amino acids, mediated by enzymes obtained from Aspergillus strains, which leads in a predictable manner to the L-amino acids 32 the o-enantiomers react very slowly250. 

Yeast-mediated reductions predominantly form a single enantiomer and it is often difficult to find conditions which produce the opposite stereoisomer selectively. It has, however, been possible to obtain both enantiomers in 50% yield in 100% via enzymatic optical resolution. Chiral fluorinated secondary alcohols possessing the mono-, di- and/or trifluoromethyl group have been prepared by enzyme-catalyzed kinetic resolutions [27]. 

Reactions catalyzed by enzymes can be utilized for this kind of resolution.136... 

Most NAD+- or NADP+- dependent dehydrogenases are dimers or trimers of 20- to 40-kDa subunits. Among them are some of the first enzymes for which complete structures were determined by X-ray diffraction methods. The structure of the 329-residue per subunit muscle (M4) isoenzyme of lactate dehydrogenases (see Chapter 11) from the dogfish was determined to 0.25 nm resolution by Rossmann and associates in 1971.2 1 More recently, structures have been determined for mammaliam muscle and heart type (H4) isoenzymes,5 for the testicular (C4) isoenzyme from the... 

ENANTIOMERICALLY PURE ETHYL (R)- AND (S)-2-FLUOROHEXANOATE BY ENZYME-CATALYZED KINETIC RESOLUTION (Hexanolc acid, 2-1luoro-, ethyl ester, (R)- and (S)-)... 

This method represents a resolution by asymmetric enzymic synthesis (e.g. l-alanine, H2N,CH(CH3)-C02H, Expt 5.221). Related procedures involve other types of enzymic reactions (e.g. hydrolysis, oxidation, etc.). Asymmetric enzymic hydrolysis, for example, proceeds according to the following reaction sequence. 

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