Chemistry Reference
In-Depth Information
Rhodococcus erythropolis
whole-cell catalyst,
containing
nitrile hydratase and amidase
Ph
O
O
Ph
O
O
+
R
OH
R
NH
2
72
47-50% yield
Up to 94.4% ee
73
41-50% yield
Up to >99.5% ee
Ph
X
rac
CN
R
rac
-
70
(X=O)
rac
-
71
(X=NH)
Ph
NH
O
Ph
NH
O
+
R
OH
R
NH
2
74
45-50% yield
Up to >99.5% ee
75
44-47% yield
Up to >99.5% ee
Rhodococcus erythropolis
whole-cell catalyst,
containing
nitrile hydratase and amidase
Scheme 6.28.
[99,100]. A representative example is the successful synthesis of L-α - methyl - 3,4 -
dihydroxyphenylalanine. Other types of racemic α-methylated amides have been suc-
cessfully resolved as well. Furthermore, biocatalytic resolution of α - amino acids bearing
two stereogenic centers has been done by means of amidases, and was applied, for
example, for the synthesis of an intermediate of the pharmaceutically important antibiot-
ics fl orfenicol and thiamphenicol [101].
An amidase-catalyzed resolution was also the key step in the synthesis of highly
enantiomerically enriched β - hydroxy and β - amino acids
72
and
74
, and amides
73
and
75
reported by the Wang group [102]. Therein, a wild-type microorganism, namely
Rhodococcus erythropolis
AJ270, containing a nitrile hydratase and an amidase was used
as biocatalyst. The initial step is a transformation of the racemic nitrile
rac
-
70
and
rac
-
71
into the amide catalyzed by the nitrile hydratase followed by amidase-catalyzed amide
hydrolysis. The enantioselectivity was caused predominantly by the amidase. Notably,
O
- and
N
-benzyl protection of the substrates turned out to be a key prerequisite for
high enantioselection. The corresponding products
72
,
73
,
74
, and
75
are obtained in
high yield and with enantioselectivities of up to 94.4% ee and >99.5% ee, respectively
(Scheme 6.28 ).
6.3.5. Hydantoin Hydrolysis
A further versatile category of substrate for enzymatic resolution is racemic hydantoins:
In the presence of hydantoinases and carbamoylases, racemic hydantoins
rac
-
76
are
enantioselectively converted into enantiomerically pure α - amino acids [80,103] . In the
initial step, the hydantoinase catalyzes the hydrolytic ring opening of the hydantoin
under (reversible) formation of an
N
-carbamoyl amino acid. Subsequent cleavage of the
N
-carbamoyl amino acid of type
77
furnishes the desired α - amino acid, L - or D -
63
. This
step is irreversible and is known to proceed with excellent enantioselectivity. Racemiza-
tion of the hydantoin allows a dynamic kinetic resolution process. For racemization, a
hydantoin racemase can be used. Alternatively, some hydantoins also racemize
in situ
