Dynamic kinetic resolution of racemic ketones through asymmetric reduction

1 Dynamic kinetic resolution of racemic ketones through asymmetric reduction 

Dynamic kinetic resolution of racemic ketones can be achieved through asymmetric reduction. For example, baker s yeast reduction of (J /S)-2-(4-methoxyphenyl)-l,5-benzothiazepin-3,4(2H,5H)-dione gave only one out of four possible isomers as shown in Fig. 10.42(a).Only (S)-ketone was recognized by the enzyme as a substrate and reduction of the ketone proceeded diastereoselectively to give the enantiomericaUypure (2S.3S)-alcohol. The resulting product was used for the synthesis of (2S,3S)-diltiazem, a coronary vasodilator. 

Dynamic kinetic resolution of a -alkyl-jS -keto esters was conducted successfully using biocatalysts (Fig. 10.42(b)).For the reduction of ethyl 2-methyl-3-oxobutanoate, a method of extensive screening was used to find the suitable microorganism. As a result, Klebsiella pneumoniae IFO 3319, out of 450 bacterial strains, was found to give the corresponding (2i ,3S)-hydroxy ester with 99% de and 99% ee in kilogram scale quantitatively. 

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DYNAMIC KINETIC RESOLUTION OF RACEMIC KETONES THROUGH ASYMMETRIC REDUCTION... 

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