Chemistry Reference
In-Depth Information
Nitrilase from
Alcaligenes faecalis
,
buffer, pH 8.0
OH
OH
rac
CN
CO
2
H
+2 H
2
O,
-NH
3
rac
-
55
(
R
)
-
57
91% yield
>99% ee
O
H
+
HCN
56
Scheme 6.21.
Evolved (
R
)-nitrilase,
buffer, 20°C
OH
OH
NC
CN
NC
CO
2
H
+2 H
2
O,
-NH
3
58
(Substrate conc.:
3M)
(
R
)
-
59
96% yield
98.5% ee
Scheme 6.22.
Nitrilase from
Arabidopsis
thaliana
CN
rac
CN
CN
CN
i
-Pr
i
-Pr
i
-Pr
+
+2 H
2
O,
-NH
3
CO
2
H
CN
rac
-
60
(
S
)
-
61
45% yield
>97% ee
(
R
)
-
60
Scheme 6.23.
Furthermore, nitrilases can also catalyze enantioselectively the hydrolysis of α - amino
nitriles under formation of optically active amino acids. Using a nitrilase of
Rhodococcus
rhodochrous
, Furuhashi et al. reported the formation of L-leucine with an enantiomeric
excess of about 97% ee with racemic aminoisocapronitrile as a starting material [76].
A further highlight in nitrilase-based asymmetric synthesis is the preparation of a key
intermediate for a second generation process for pregabalin (Scheme 6.23) [64]. Starting
from a racemic dinitrile
rac
-
60
regio- and enantioselective hydrolysis delivered the cor-
responding acid (
S
) -
61
in 45% yield and with an excellent enantiomeric excess of > 98%
ee. Notably, the remaining undesired enantiomer (
R
) -
61
can be easily recycled. Thus,
the overall yield of pregabalin is increased from 18% to 21% in the original process
[77] up to 40% (after one recycling) in this biocatalytic second generation process
[64]. Notably, a further effi cient biocatalytic synthetis route toward pregabalin based
