Chemistry Reference
In-Depth Information
Reductions based on the use of ADH and FDH already proved their technical fea-
sibility. This has been successfully demonstrated by the Patel group in the production
of (
S
) - 2 - pentanol ((
S
) -
131
) on pilot scale using an ADH from
Gluconobacter oxydans
(SC 13851) [208].
G. oxydans
cells, pretreated with Tritone X-100, were used as biocata-
lyst in combination with the FDH from
C. boidinii
. This reduction was carried out at a
1.500-L scale with a substrate input of 3.2 kg (
2.13 g/L). The desired (
S
) - 2 - pentanol
((
S
) -
131
) has been formed with a conversion of 32.2% and an enantioselectivity of
∼
>
99%
ee (Scheme 6.52 ).
(
S
)-alcoholdehydrogenase
(
Gluconobacter oxydans
cells,
pretreated with Triton X-100),
formate dehydrogenase
(
Candida boidnii
)
O
OH
H
3
C
CH
3
H
3
C
CH
3
NAD
+
, NaHCO
2
130
(
S
)-
131
32.2% conversion
>9 9% ee
Scheme 6.52.
The potential of an FDH-based whole-cell catalyst for synthetic applications has been
recognized by Matsuyama et al., constructing a recombinant
E. coli
W3110 strain, which
coexpresses an ADH from
Pichia fi nlandica
and an FDH from
Mycobacterium
[209] .
The tailor-made whole-cell catalyst has been successfully applied, for example, in the
enantioselective reduction of ethyl 4 - chloro - 3 - oxobutanoate (
122
) under the formation
of the corresponding (
S
) - alcohol (
S
) -
123
at 32.2 g/L substrate input with 98.5% yield and
99% ee (Scheme 6.53 ).
OH
O
Cl
HCO
2
OEt
NAD
(
S
)-
123
98.5 yield
99% ee
Tailor-
made
whole-cell
catalyst
Formate
dehydrogenase
Alcohol
dehydrogenase
O
O
Cl
CO
2
NADH
OEt
122
Substrate input:
32.2 g/L
Scheme 6.53.
