Chemistry Reference
In-Depth Information
Corynebacterium equi
whole-cell catalyst
containing
monooxygenase,
NAD(P)
+
O
n
-C
12
H
25
n
-C
12
H
25
+O
2
185
(
R
)-
186
41% yield
>9 9% ee
Scheme 6.80.
Bacillus megaterium
whole-cell catalyst
containing
monooxygenase,
NAD(P)
+
OH
OH
Me
Me
Me
Me
Me
Me
+
Me
+
Me
+D-glucose,
+O
2
(Ratio of
188
:
189
:
190
:
9:3:1)
187
OH
(
S
)-
188
>99% ee
190
6% ee
(
S
)-
189
>99% ee
Scheme 6.81.
The enantioselectivity of monooxygenases has been improved by the Arnold group
[314]. Applying an engineered cytochrome P450 BM-3 enzyme to the epoxidation of
several terminal aliphatic alkenes led to enantioselectivities between 55% ee and
83% ee. Notably, inversion of enantioselectivity in the epoxidation of styrene has been
achieved by the Schwaneberg group by means of a single mutation in the P450 BM3
monooxygenase [315]. This mutant was found via directed evolution
Furthermore, a regio- and enantioselective epoxidation of linolenic has been devel-
oped by the Turner group using a P450-monooxygenase from
B. megaterium
[316] . In
the presence of this biocatalyst, an enantioselectivity of 60% ee was obtained.
6.6.4. Hydroxylation of Alkanes
Selective functionalization of alkanes is still among the most current challenges in the
fi eld of organic chemistry. Enzymes, namely monooxygenases, turned out to be versatile
and selective catalysts [317 - 319] . In some fi elds, in particular related to steroid hydrox-
ylation, technical applications have already been reported [320]. In the following, a brief
overview of main achievements in asymmetric enzymatic hydroxylation in recent years
will be given. It is noteworthy that in spite of excellent selectivities for many oxidore-
ductase-catalyzed reactions (e.g., reductions with ADHs; see Section 6.5.2), highly asym-
metric hydroxylation protocols are still rare.
Pioneer work in the fi eld of asymmetric hydroxylation has been done by the Adam
group [321]. When using a
B. megaterium
strain as a whole-cell biocatalyst, asymmetric
hydroxylation proceeds with a range of linear
n
- alkanes such as
n
- heptane and
n
- octane
(
187
) in a highly enantioselective fashion. However, regioselectivity still needs improve-
ment since different types of regioisomers are formed in signifi cant amount. Further-
more, undesired “overoxidation” under formation of the corresponding ketones from
the alcohols plays a role. An example for the formation of regiosiomers with up to
>
99%
ee is shown in Scheme 6.81.
