Dynamic Kinetic Resolutions Based on Reduction Processes

Dynamic Kinetic Resolutions Based on Reduction Processes 

The racemization of the unreacted substrate can be accomplished either by spontaneous equilibration between the two enantiomers or by using a chemical or biological catalyst. The basic requirements for a successful DKR are that (i) the KR conditions must be compatible with the racemization process, (ii) the KR process must be very stereoselective, (iii) the catalyst for the racemization must not react with the product, and (iv) the racemization must be faster than the reaction of the slow reacting enantiomer k c 2 ksiow [la,b]. The concept of DKR has been applied to a variety of compounds such as a-amino acids, hemithioacetal esters, a-(hetero) arylcarboxylic acids, a-substituted nitriles, beta-keto esters, cyanohydrin esters, a-substituted thioesters, 4-substituted oxazolin-5-ones and thiazolin-5-ones [la]. 

Synthetic Methods for Biolo cally Active Molecules Exploring the Potential of Bioreductions, First Edition. Edited by Elisabetta Brenna, 

Historically, this term was applied for the first time by Noyori [2], in the case of a ruthenium-catalyzed hydrogenation of a-substituted-P-keto esters. According to Noyori and his coworkers, even when the racemization constant k ac is the same as the rate constant of the fast reacting enantiomer, good enantioselectivities and quantitative conversions can be obtained [3]. An efficient DKR process can also be obtained when krac is higher than the rate constant of the reduction of the slow reacting enantiomer (krac fesiow)- 

Various examples were described, including whole cell-biocatalyzed reductions [4], especially employing baker s yeast [la,5]. However, there was always the problem that several active enzymes with different selectivities were present, although in particular cases excellent conversions and stereoselectivities were achieved. Later on, by directed evolution techniques [6], improvement of stereoselectivities and substrate specificities of enzymes was achieved, as well as several enzymatic properties (e.g., thermal stability) were modified. Moreover, large amounts of biocatalysts have been produced by fermentation of recombinant bacteria that express the gene, when their corresponding DNA has been doned. The drawback of the expensive cofactor recyding has also been overcome by the devdopment of effident techniques [7]. 

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I 72 Dynamic Kinetic Resolutions Based on Reduction Processes... 

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