ADH, Alcohol dehydrogenase
Dehydrogenases are used as enzymes for the oxidation and reduction of carbonyl groups, respectively alcohols. The enzymes are mostly NAD(P)H-dependent. For the reduction of aldehydes and ketones, baker yeast is often used.
Reductions with isolated enzymes: During the reduction of a carbonyl group, the cofactor NAD(P)H - the hydride donor - must be stoichiometrically used, or being regenerated through in situ reduction of NAD(P)+ because of the high costs during the reaction.
A possibility for the recycling of NAD(P)H is the use of a second enzyme and a suitable substrate which is oxidized : glucose / glucose dehydrogenases, glucose-6-phosphate / glucose-6-phosphate dehydrogenases and alcohol / alcohol dehydrogenases.
Formate dehydrogenase is common used as enzyme for the oxidation of formic acid to CO2 for the recovery of NADH from NAD. This method is often used with the reduction of carbonyl groups to alcohols and amines but, however, cannot be used for the recovery of NADPH.
In a biphasic reaction media for the asymmetric biocatalytic reduction of ketones with in situ cofactor regeneration, both enzymes (ADH and FDH) remain stable. Reductions with poorly water-soluble ketones were carried out at substrate concentrations of > 10 mM, and alcohols were formed with good conversions in high enantioselectivity.
H. Groeger, W. Hummel, S. Buchholz, K. Drauz, T. V. Nguyen, C. Rollmann, H. Huesken, K. Abokitse, Org. Lett., 2003, 5, 173-176.
By careful selection of appropriate enzymes (alcohol dehydrogenases [ADH] and cofactor recycling enzymes), cofactor recycling of NADH can be performed in the presence of NADP+ recycling to achieve overall (R)- or (S)-selective deracemisations of sec-alcohols or stereoinversion representing a possible concept for a “green” equivalent to the chemical-intensive Mitsunobu inversion.
C. V. Voss, C. C. Gruber, K. Faber, T. Knaus, P. Macheroux, W. Kroutil, J. Am. Chem. Soc., 2008, 130, 13969-13972.
Sphingomonas paucimobilis NCIMB 8195 catalyzes an efficient deracemization of a wide range of secondary alcohols leading to up to 90% yield of the (R)-alcohol. The corresponding ketones were formed at various levels during each of the biotransformations, indicating that stereoinversion of the (S)-alcohol proceeds by sequential oxidation and reduction.
G. R. Allan, A. J. Carnell, J. Org. Chem., 2001, 66, 6495-9497.