Dynamic stereoinversion

Biooxidative deracemization of racemic sec-alcohols to single enantiomers [47,48] is complementary to combined metal-assisted lipase-mediated strategies [49,50]. In general, deracemization can be realized by either an enantioconvergent, a dynamic kinetic resolution, or a stereoinversion process. The latter concept is particularly appealing, as only half of the substrate needs to be converted, as the remaining half already represents the product with correct stereochemistry. 

Biocatalytic Deracemization Dynamic Resolution, Stereoinversion, Enantioconvergent Processes and Cyclic Deracemization, in Biocatalysts in the Pharmaceutical and Biotechnology industries, (ed. R.N. Patel), CRC Press, Boca Raton, pp. 27-51. 

Pellissier, H., Recent developments in dynamic kinetic resolution. Tetrahedron, 2008, 64, 1563-1601 Turner, N.J., Enzyme catalysed deracemisation and dynamic kinetic resolution reactions. Curr. Opin. Chem. Biol., 2004, 8, 114-119 Gmber, C.C., Lavandera, I., Faber, K. and Kroutil, W., From a racemate to a single enantiomer deracemisation by stereoinversion. Adv. Synth. Catal., 2006, 348, 1789-1805 Pellissier, H., Dynamic kinetic resolution. Tetrahedron, 2003, 59, 8291-8327 Pmnies, O. and Backvall, J.-E., Combination of enzymes and metal catalysts. A powerful approach in asymmetric catalysis. Chem. Rev., 2003, 103, 3247-3261. 

Such conventional kinetic resolution reported above often provide an effective route to access to the enantiomerically pure/enriched compounds. However, the limitation of such process is that the resolution of two enantiomers will provide a maximum 50% yield of the enantiomerically pure materials. Such limitation can be overcome in several ways. Among these ways are the use of meso compounds or prochiral substrates,33 inversion of the stereochemistry (stereoinversion) of the unwanted enantiomer (the remaining unreacted substrate),34 racemization and recycling of the unwanted enantiomer and dynamic kinetic resolution (DKR).21... 

Stecher, H. Faber, K. Biocatalytic deracemization techniques. Dynamic resolutions and stereoinversions. Synthesis 1997, 1, 1-16. 

Free energies of activation for the enantiomerization of a series of iV-aryl-1,3,2-benzodithiazole 1-oxides 41 have been determined by dynamic high-performance liquid chromatography (DHPLC) on a chiral stationary phase <1999JOC1483>. From a comparison of experimental and computer-simulated chromatograms, the barriers to stereoinversion at sulfur were found to be around 80 kj mol 1 and relatively insensitive to effects from substituents in the iV-aryl group. 

Azerad, R., and Buisson, D. 2000. Dynamic resolution and stereoinversion of secondary alcohols by chemo enzymatic processes. Curr. Op. Biotechnol., 11(6), 565-571. 

The two more common strategies for achieving such an objective are deracemization by stereoinversion or deracemization by dynamic kinetic resoluhon DKR (Scheme 13.1). 

In addition, reviews dealing with aspects of enzyme-catalyzed dynamic resolution and related processes such as stereoinversion and deracemisation have also been published[4 71. Details of the kinetic principles of dynamic kinetic resolution reactions have also been reported,7 9). Interestingly, a dynamic kinetic resolution reaction can provide a product with higher enantiomeric excess than the corresponding kinetic resolution. In a conventional kinetic resolution, the enantiomeric excess of the product often decreases as a function of conversion. This happens because as the reaction proceeds, the proportion of the preferred enantiomer of substrate decreases. Unless the enzyme is able to discriminate perfectly between the substrate enantiomers, it will catalyze the reaction of the less preferred enantiomer of substrate (the proportion of which grows as the reaction proceeds). However, in a dynamic kinetic resolution where the substrate enantiomers are interconverting rapidly, the ratio of substrate enantiomers will be constant at 1 1. Consequently, the enantiomeric excess of the product will not decrease as the reaction proceeds. 

Simeo Y, KrontU W, Paber K. Biocatalytic deracemization dynamic resolution, stereoinversion, enantioconvergent processes, and cyclic deracemization. In Biocatalysis in the Pharmaceutical and Biotechnology Industries, Ed. Patel RN. CRC Press, Boca Raton, PL, 2007, p. 27. 

Stecher, H., and Faber, K. (1997) Biocatalytic Deracemization Techniques. Dynamic Resolutions and Stereoinversions, Synthesis 1,1-16. 

The first edition of this book appeared in September 1992 and was predominantly composed as a monograph. It was not only well received by researchers in the field but also served as a basis for courses in biotransformations worldwide, fii the second, completely revised edition, emphasis was laid on didactic aspects in order to provide the first textbook on this topic in 1995. Its great success has led to the demand for updated versions with emphasis on new trends and developments. In this context, novel techniques - dynamic resolution, stereoinversion, and enan-tioconvergent processes - were incorporated, in addition to the basic rules for the handling of biocatalysts. 

For a long time, kinetic resolution of alcohols via enantioselective oxidation or via acyl transfer employing, for example, lipases along with dynamic kinetic resolution have been the biocatalytic methods of choice for the preparation of chiral alcohols. In recent years, however, impressive progress has been made in the use of alcohol dehydrogenases (ADHs) and ketor-eductases (KREDs) for the asymmetric synthesis of alcohols by stereoselective reduction of the corresponding ketones. Furthermore, recent remarkable multienzymatic systems have been successfully applied to the deracemisation of alcohols via stereoinversion based on an enantioselective oxidation followed by an asymmetric reduction. 

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