Chemistry Reference
In-Depth Information
desired alcohols, for example, (
R
) -
135
, with good to high enantioselectivities. Both ADH
and GDH were used in an immobilized form. The conversions of these enzymatic bio-
transformations were in the range of 72-90%. Although enantioselectivities varied, they
exceeded 90% ee in many cases. A selected example is shown in Scheme 6.55.
OH
CF
3
irreversible
D-gluconic
acid
D-glucono-
lactone
NAD(P)
(
R
)-
135
94 % ee
Glucose dehydrogenase
from
Bacillus cereus
Alcohol dehydrogenase
from
Thermoanaerobium brockii
O
CF
3
NAD(P)H
D-glucose
134
Scheme 6.55.
A recent contribution to this fi eld has been made by the Hua group focusing on the
asymmetric reduction of
-chlorinated ketones in the presence of isolated ADHs and
under regeneration of the cofactor with a GDH [216]. A range of
α
- chlorinated alcohols
were formed in high yields of 72-99%, and with excellent enantioselectivities of typically
α
>
99% ee. The joint use of ADH and GDH has also been successfully applied for the
enantioselective reduction of substituted benzophenones by Merck researchers [217].
The feasibility of this methodology for an enantio- and diastereoselective reduction of
ethyl 6-benzyloxy-3,5-dioxohexanoate, has been demonstrated by the Patel group
[218,219]. When using cell extracts of
Acinetobacter calcoaceticus
in combination with a
GDH and glucose, the desired product ethyl (3
R
,5
S
) - 6 - benzyloxy - 3,5 - dihydroxyhexano-
ate ((3
R
,5
S
) -
137
) was formed with 92% conversion and an enantioselectivity of 99% ee
(Scheme 6.56). After product isolation, (3
R
,5
S
) -
137
was obtained in 72% yield and with
an enantiomeric excess of 99.5% ee.
ADH from
Acinetobacter
calcoaceticus
OOO
OH
OH
O
O
O
O
e
O
e
GDH,
glucose, NAD
+
,
92% conversion
136
(3
R
,5
S
)-
137
72% yield
99.5% ee
Scheme 6.56.
