2.2.2 Reduction of Aldehydes and Ketones Using Isolated
Enzymes
A broad range of ketones can be reduced stereoselectively using dehydrogenases to
furnish chiral secondary alcohols [847–850]. During the course of the reaction, the
enzyme delivers the hydride preferentially either from the si- or the re-side of the
ketone to give (R)- or (S)-alcohols, respectively. The stereochemical course of the
reaction, which is mainly dependent on the steric requirements of the substrate, may
be predicted for most dehydrogenases from a simple model which is generally
referred to as ‘Prelog’s rule’ (Scheme 2.112) [851].
It is based on the stereochemistry of microbial reductions using Curvularia
falcata cells and it states that the dehydrogenase delivers the hydride from the reface of a prochiral ketone to furnish the corresponding (S)-configured alcohol. The
majority of the commercially available dehydrogenases used for the stereospecific
reduction of ketones [such as yeast alcohol dehydrogenase (YADH), horse liver
alcohol dehydrogenase (HLADH)] and the majority of microorganisms (for
instance, baker’s yeast) follow Prelog’s rule [852]. Thermoanaerobium brockii
alcohol dehydrogenase (TBADH) also obeys this rule when large ketones are
used as substrates, but the stereopreference is reversed with small substrates.
Microbial dehydrogenases which lead to the formation of anti-Prelog configurated
(R)-alcohols are known to a lesser extent, and even fewer are commercially
available, e.g., from Lactobacillus sp. [853–855]. Other ADHs from Curvularia
OH
O
CIP sequence order of L > S assumed
'Prelog´s Rule'
large
NAD(P)H
NAD(P)
+
Dehydrogenase
S
[H - ]
small
small
large
Dehydrogenase
Specificity Cofactor Commercially
available
yeast-ADH
Prelog
NADH
+
horse liver-ADH
Prelog
NADH
+
Thermoanaerobium brockii-ADH Prelog a
NADPH
+
Hydroxysteroid-DH
Prelog
NADH
+
Rhodococcus ruber ADH-A
Prelog
NADH
+
Rhodococcus erythropolis ADH Prelog
NADH
+
Candida parapsilosis-ADH
Prelog
NADH
+
Lactobacillus brevis ADH
anti-Prelog NADPH
+
Lactobacillus kefir-ADH
anti-Prelog NADPH
+
Mucor javanicus-ADH
anti-Prelog NADPH
-
Pseudomonas sp.-ADH
anti-Prelog NADH
-
a Anti-Prelog specificity on small ketones.
Scheme 2.112 Prelog’s rule for the asymmetric reduction of ketones
140
2 Biocatalytic Applications
Enzymes
A broad range of ketones can be reduced stereoselectively using dehydrogenases to
furnish chiral secondary alcohols [847–850]. During the course of the reaction, the
enzyme delivers the hydride preferentially either from the si- or the re-side of the
ketone to give (R)- or (S)-alcohols, respectively. The stereochemical course of the
reaction, which is mainly dependent on the steric requirements of the substrate, may
be predicted for most dehydrogenases from a simple model which is generally
referred to as ‘Prelog’s rule’ (Scheme 2.112) [851].
It is based on the stereochemistry of microbial reductions using Curvularia
falcata cells and it states that the dehydrogenase delivers the hydride from the reface of a prochiral ketone to furnish the corresponding (S)-configured alcohol. The
majority of the commercially available dehydrogenases used for the stereospecific
reduction of ketones [such as yeast alcohol dehydrogenase (YADH), horse liver
alcohol dehydrogenase (HLADH)] and the majority of microorganisms (for
instance, baker’s yeast) follow Prelog’s rule [852]. Thermoanaerobium brockii
alcohol dehydrogenase (TBADH) also obeys this rule when large ketones are
used as substrates, but the stereopreference is reversed with small substrates.
Microbial dehydrogenases which lead to the formation of anti-Prelog configurated
(R)-alcohols are known to a lesser extent, and even fewer are commercially
available, e.g., from Lactobacillus sp. [853–855]. Other ADHs from Curvularia
OH
O
CIP sequence order of L > S assumed
'Prelog´s Rule'
large
NAD(P)H
NAD(P)
+
Dehydrogenase
S
[H - ]
small
small
large
Dehydrogenase
Specificity Cofactor Commercially
available
yeast-ADH
Prelog
NADH
+
horse liver-ADH
Prelog
NADH
+
Thermoanaerobium brockii-ADH Prelog a
NADPH
+
Hydroxysteroid-DH
Prelog
NADH
+
Rhodococcus ruber ADH-A
Prelog
NADH
+
Rhodococcus erythropolis ADH Prelog
NADH
+
Candida parapsilosis-ADH
Prelog
NADH
+
Lactobacillus brevis ADH
anti-Prelog NADPH
+
Lactobacillus kefir-ADH
anti-Prelog NADPH
+
Mucor javanicus-ADH
anti-Prelog NADPH
-
Pseudomonas sp.-ADH
anti-Prelog NADH
-
a Anti-Prelog specificity on small ketones.
Scheme 2.112 Prelog’s rule for the asymmetric reduction of ketones
140
2 Biocatalytic Applications