Chemistry Reference
In-Depth Information
on a lipase-catalyzed resolution via hydrolysis has also been developed by Tao et al.
recently [78] .
6.3.4. Amide Hydrolysis
Enantioselective resolution of racemic amides belongs to the most important biotrans-
formations in the fi eld of enantioselective amino acid synthesis. In general, two types of
amides can be used as substrates, namely
N
- acylated amino acids or amino acid amides.
Both substrates can be easily prepared on large scale as well. For hydrolysis of
N
-
acylated amino acids, aminoacylases or penicillin acylases are the enzymes of choice,
whereas amidases are used in case of amino acid amides. Both resolution techniques are
applied on large scale and represent key industrial technologies for the technical produc-
tion of L- and D-amino acids.
To start with the aminoacylase-catalyzed resolution of racemic
N
- acetyl α - amino
acids,
rac
-
62
, this methodology is robust and highly effi cient. An impressive study on the
substrate range by Whitesides et al. revealed that amino acylases I from porcine kidney
and
Aspergillus oryzae
tolerate a broad range of aliphatic, aromatic, and heteroaromatic
substrates, leading to the desired L-amino acids of type L-
63
in good yields and with
excellent enantiomeric excess of
99% ee in many cases [79]. Selected examples of this
type of resolution for the synthesis of L-amino acids (
S
) -
63
are shown in Scheme 6.24.
>
O
O
L-aminoacylase I
water, pH 7.5-8.0
H
3
C
NH
NH
2
H
3
C
NH
rac
+
R
CO
2
H
R
CO
2
H
R
CO
2
H
+H
2
O
rac
-
62
-CH
3
CO
2
H
(
R
)-
62
(
S
)-
63
Selected examples of suitable substrates
O
O
O
O
H
3
C
NH
H
3
C
NH
H
3
C
NH
H
3
C
NH
rac
H
3
C
rac
rac
rac
CO
2
H
H
3
C
H
3
C
CO
2
H
CO
2
H
CO
2
H
CH
3
rac
-
62a
rac
-
62b
rac
-
62d
rac
-
62c
Scheme 6.24.
Due to the high process effi ciency, the amino acylase technology has been industrially
applied for decades on a several hundred ton scale [80]. An elegant technical
concept developed by Wandrey, Kula and Leuchtenberger et al. represents the enzyme
membrane reactor (EMR), which is applied at Degussa AG (now Evonik Degussa
GmbH) for the manufacture of L-methionine [81,82]. In a continuous resolution
process in homogeneous solution, the enzyme cleaves enantioselectively the L-
N
- acetyl
methionine under formation of the desired L-amino acid L-methionine. Due to its
high effi ciency, amino acylases-type resolution has become a widely applied
