Chemistry Reference
In-Depth Information
Saccharomyces cerevisiae
whole-cell catalyst
containing
cyclohexanone
monooxygenase,
NADP
+
O
O
O
Et
rac
Et
O
+
Et
+O
2
rac
-
175
(
S
)-
176
79% yield
95% ee
(
R
)-
175
69% yield
>9 8% ee
Scheme 6.75.
shown in Scheme 6.75. Further examples of successful applications of Baeyer-Villiger
monooxygenases in resolution processes have been described by several groups for the
resolution of racemic bicyclic ketones [296 - 298] .
Due to the high effi ciency of enzymatic Baeyer-Villiger reactions and availability of
a recombinant production strain of the biocatalyst, scale-up of this methodology has
been reported as well [299]. For example, a biotransformation at kilogram scale has been
reported by Furstoss and coworkers in collaboration with Sigma-Aldrich for the enzy-
matic Baeyer- Villiger oxidation of racemic bicyclo[3.2.0]hept - 2 - en - one (
rac
-
177
) in a
50-L bioreactor. Besides a high productivity, high enantioselectivities were obtained for
both regioisomeric lactones (1
S
,5
R
) -
178
and (1
R
,5
S
) -
179
when operating at a substrate
input of 25 g/L (Scheme 6.76 ) [300] .
E. coli
whole-cell catalyst
containing
cyclohexanone
monooxygenase,
NADP
+
O
O
O
O
+
O
Glycerol, O
2
,
adsorbent resin,
pH 7, 37°C,
100% conversion,
60% overall yield
of lactones
rac
-
177
(25 g/L
substrate input)
(1
S
,5
R
)-
178
97.4% ee
(1
R
,5
S
)-
179
>99% ee
Scheme 6.76.
As a very nice extension of the enzymatic Baeyer-Villiger oxidation, Alphand et al.
reported a combination of this reaction (as a resolution) with an anion-exchange resin-
catalyzed racemization of the substrate toward a dynamic kinetic resolution process
[301]. High yields of up to 85% accompanied by excellent enantioselectivities of up to
97% ee were achieved when using racemic benzyloxycyclopentanone as a substrate.
A further process improvement with respect to the type of cofactor recycling was
reported by the Willetts group. By coupling a cyclohexanone monooxygenase with an
ADH from
T. brockii
, a cosubstrate - free “ double oxidation ” of an alcohol
endo
-
180
into
lactones
178
and
179
is achieved (Scheme 6.77) [302]. The oxidized form of the cofactor
