Dynamic kinetic bioreduction

Merck scientists reported a practical enantioselective synthesis of cis-2,5-disubstituted pyrrolidines where the key chiral step 3 is a dynamic kinetic bioreduction as shown in Scheme 6.29. The bioreduction is performed at pH 7 and 30 °C using GDH as the cofactor recycle system yielding 99% ee and more than 90% assayed yield [43]. 

Dynamic kinetic bioreduction to access chiral hydroxyl amino esters. 

Alkyl-4-oxy-3,4-dihydroisocoumarins are enantioselectively prepared by oxylactonization ofo-(alk-l-enyl)benzoates promoted by the in situ-generated chiral lactate-based hypervalent iodine(III) catalysts (13EJ07128). Chemoenzymatic synthesis of 3,4-dialkyl-3,4-dihydroisocoumarins involves one-pot dynamic kinetic reductive resolution processes catalyzed by E. co/i/alcohol desidrogenase. This strategy consists in the bioreduction of various racemic ketones to the corresponding enantiopure alcohols followed by intramolecular acidic cyclization (Scheme 71) (130L3872). 

The dynamic kinetic resolution (DKR) approach to obtain an enantiomerically pure product is based on the in situ racemization of the starting material, together with the selective bioreduction of one substrate enantiomer (Scheme 4.12). These... 

Scheme 12.15 Dynamic kinetic resolution in the bioreduction of a-alkyl-P-keto esters by Recombinant E. co//expressing Gcylp or Cre3p.

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