Chemistry Reference
In-Depth Information
1. 60
°C, 30h,
95.0% conv.
O
Ph
NH
O
Ph
NH
O
Step 1
OEt
+
Ph
NH
2
OEt
+
Me
H
Ph
Me
Me
35
(2.2 equiv)
2. Lipase CAL-B,
60°C, 18h,
59.8% conv.
37
(
S
)-
38
36% yield
99% ee
(
R
)-
39
55% yield
60% ee
Step 2
Scheme 6.13.
O
O
Lipase CCL,
RNH
2
O
PPh
3
Cl
Me
Me
Me
OEt
OEt
NHR
Cl
Cl
Cl
(
R
)-
40
(
S
)-
40
(
S
)-
41
Up to 92 % yield
Up to 86% ee
Scheme 6.14.
cylindracea
(CCL), aminolysis led to the formation of the desired amides (
S
) -
41
in yields
of up to 92% and with enantiomeric excess of up to 86% ee (Scheme 6.14).
6.3. HYDROLYTIC REACTIONS
6.3.1. Overview
Besides their use in acylation reactions (see Section 6.2), hydrolases are very useful cata-
lysts for the hydrolysis of carboxylic acid derivatives, in particular esters and amides.
The hydrolysis of esters has been applied not only for the resolution of racemic carboxylic
esters but also for the desymmetrization of prochiral diesters such as malonates or
meso
-
compounds bearing two ester moieties. Although ester hydrolysis is probably the most
frequently applied hydrolytic transformation with hydrolases, hydrolysis of other func-
tional groups plays a role as well. The hydrolysis of nitriles to carboxylic acids turned
out to be a versatile approach toward
- amino acids. Notably, this
process can be carried out as a dynamic kinetic resolution since racemization of the
substrate proceeds easily under the applied reaction conditions. Furthermore, hydrolysis
of amide bonds plays a very important role in the fi eld of enantioselective amino acid
synthesis. Notably, hydrolytic reaction can proceed at the acid amide moiety (with ami-
dases) as well as at the
N
-acylated amino functionality (by using aminoacylases). Both
routes are highly effi cient and are widely applied already on technical scale in the fi ne
chemicals industry for the synthesis of chiral amino acids. Racemases are available for
both of these processes, which make dynamic kinetic resolutions possible. Another
dynamic kinetic resolution for amino acid production by means of hydrolytic enzymes
α
- hydroxy acids and
α
