Chemistry Reference
In-Depth Information
Methylobacterium
sp
whole-cell catalyst
containing
epoxide hydrolase
n
-C
5
H
11
n
-C
5
H
11
n
-C
5
H
11
Me
Me
HO
Me
O
O
rac
+
HO
Buffer, pH 7.8
50% conversion
(
S
)-
87
82% yield
84% ee
rac
-
87
(
R
)-
88
H
+
cat.
Dioxane-water
0°C
Scheme 6.34.
Rhodococcus ruber
whole-cell catalyst
containing
alkylsulfatase
Buffer, pH 7.5
E = 21
OSO
3
rac
OH
OSO
3
+
n
-C
6
H
13
Me
n
-C
6
H
13
Me
n
-C
6
H
13
Me
rac
-
89
(
S
)-
90
46% conversion
82% ee
(
S
)-
89
Scheme 6.35.
Suitable epoxide hydrolases for the hydrolytic ring opening of aliphatic racemic
epoxides have been reported by the Faber group [116,117]. Notably, this methodology
also tolerates highly functionalized epoxides. A selected example is shown in Scheme
6.34. In the presence of whole-cell catalysts of
Methylobacterium
sp. bearing an epoxide
hydrolase, the resolution of epoxide
rac
-
87
proceeds with a high enantioselectivity,
which is indicated by an E value of 66. Subsequent acid-catalyzed ring opening under
inversion of confi guration delivers the diol (
S
) -
88
as sole product in 82% yield and with
an enantiomeric excess of 84% ee. The diol (
S
) -
88
has been used by the Faber group as
an intermediate in the total synthesis of the antibiotic (
R
) - fridamycin E.
Another interesting functional group for enzymatic enantioselective hydrolysis are
sulfate esters. When using racemic sulfatases, those racemic esters can be enzymatically
hydrolyzed under inversion of the absolute confi guration, whereas chemical hydrolysis
of sulfate esters proceeds under retention. The Faber group developed such an enzy-
matic resolution of racemic sulfates using whole cells of
Rhodococcus ruber
bearing an
alkylsulfatase as a catalyst [118,119]. For example, hydrolysis of
rac
-
89
gave the (
S
) -
alcohol (
S
) -
90
at 46% conversion with an enantiomeric excess of 82% ee, corresponding
to an E value of 21 (Scheme 6.35).
6.4. CARBON - CARBON BOND - FORMING REACTIONS
6.4.1. Overview
Formation of C-C bonds belongs to the most important asymmetric transformations.
Besides many highly effi cient developed chemocatalysts, biocatalysis also turned out to
