Chemistry Reference
In-Depth Information
Besides a screening for various ketones, the preparative asymmetric reduction of
benzoyl hydroxyacetone and
-tetralone in the presence of isolated ADH and GDH
enzymes has been described by BioCatalytics researchers [220]. Using the isolated ADH
enzymes in an amount of 1-7% (w/w) compared with the amount of substrate and a
catalytic amount of cofactor led to the synthesis of the optically active alcohols, for
example, (
R
) -
139
, in high yields. The reductions have been carried out at high substrate
concentrations of up to 0.75-1.4 M. A selected example is shown in Scheme 6.57.
α
O
OH
Alcohol dehydrogenase,
GDH
Cl
Cl
Glucose, NADPH
buffer / DMSO
138
(
R
)-
139
94% yield
>99% ee
Scheme 6.57.
The design of recombinant whole cells is an elegant approach toward tailor-made
(bio-)catalysts, which contain not only the cofactor “for free” but also both of the desired
enzymes, ADH and GDH, in overexpressed form. The corresponding reduction of
ketones proceeds within the cell according to the concept shown in Scheme 6.58. Advan-
tages of such a recombinant whole-cell system over the wild-type ones are the higher
amount of the desired enzymes within the cell (due to overexpression), their cost-
effective access, and excellent performance in synthetic applications. With respect to this
recombinant whole-cell concept, the pioneers in the design and application of highly
OH
O
NAD(P)
D-glucono-
lactone
Cl
OEt
(
R
)-
123
94.1% conversion
91.7% ee
GDH
E. coli
cells
ADH
O
O
Cl
D-glucose
NAD(P)H
OEt
122
(300 g/L substrate input)
Organic phase
(
n
-butyl acetate)
Aqueous phase
Scheme 6.58.
