Preparation Asymmetric Reduction of Ketones in a Biphasic Medium with an (S)‐Alcohol Dehydrogenase under in situ‐Cofactor‐Recycling with a Formate Dehydrogenase.

Abstract

Dehydrogenase. -Poorly water-soluble ketones are reduced under conditions A) in a biphasic medium. Alcohols are obtained with high enantioselectivities. The new method can be applied as a simple access to optically active alcohols on lab scale. -(GROEGER*, H.; HUMMEL, W.; ROLLMANN, C.; CHAMOULEAU, F.; HUESKEN, H.; WERNER, H.; WUNDERLICH, C.; ABOKITSE, K.; DRAUZ, K.; BUCHHOLZ, S.; Tetrahedron 60 (2004) 3, 633-640; Degussa AG, D-63403 Hanau, Germany; Eng.) -Adam

Bioreduction with Efficient Recycling of NADPH by Coupled Permeabilized Microorganisms

“…In general, cofactor recycling can be achieved by coupling a desired enzymatic reaction with an additional chemical, electrochemical, photocatalytic, or enzymatic reaction, and the enzymatic method is favored (1,5,9,13,16,17,22,32,39). Enzymatic cofactor recycling can be obtained by using "coupled-substrate" (8, 12, 30, 31) and "coupled-enzyme" (14,15,18,19,20,21,29,33,34) approaches. The latter is a more general approach and utilizes the first enzyme for the desired biotransformation and the second enzyme for cofactor regeneration.…”

“…Formate dehydrogenase (15,18) and glucose dehydrogenase (GDH) (33,34) are well-known enzymes used for regeneration of NADH and NADPH, respectively. The "coupled-enzyme" approach has been successfully used with two isolated enzymes (15,18,29,33,34) or whole cells (14,20,21) of a microorganism coexpressing the two necessary enzymes. While the use of isolated enzymes is costly, the use of whole cells depends on the availability of an intracellular cofactor which may be limiting and cannot be altered by addition of an extracellular cofactor.…”

Preparative Asymmetric Synthesis of 4,4-Dimethoxytetrahydro-2H-pyran-3-ol with a Ketone Reductase and in Situ Cofactor Recycling using Glucose Dehydrogenase

“…Enzymatic ketone reductions typically proceed highly enantioselectively under mild aqueous reaction conditions without generating harmful waste streams. Biocatalytic processes for the stereoselective reduction of ketones using either whole-cell systems [15][16][17][18][19] or isolated ketoreductases and alcohol dehydrogenases [20][21][22][23][24][25][26] have been widely reported. In process development and scale-up at Merck, the use of isolated enzymes is preferred because it allows rapid process development and consistently leads to highly productive processes.…”

“…23,24,27,28 The industrial application of redox enzymes has been limited by the need for expensive nicotinamide cofactors in stoichiometric amounts, but cost-effective methods for nicotinamide cofactor recycling have been reported. 25,29,30 In this contribution, we describe the enzymatic asymmetric reduction of 4,4-dimethoxytetrahydro-2H-pyran-3-one, 1, including an in situ nicotinamide adenine dinucleotide phosphate (NADPH) cofactor regeneration system that employs glucose dehydrogenase (GDH) to reduce the cost of the expensive cofactor. 31 GDH is often active on substrates that are structurally similar to glucose (as is compound 1), causing significant loss of product enantiopurity.…”