Chemistry Reference
In-Depth Information
O
O
OH
O
L-threonine aldolase
H
+
OH
OH
PLP,
buffer,
pH 8, 25°C
NH
2
NH
2
MeO
2
S
MeO
2
S
112
110
L-
threo
-
113
68% yield
53% de (
threo
/
erythro
)
>99% ee
Scheme 6.44.
substrates and lead to the formation of diastereo- and enantiomerically pure
α
- amino
β
- hydroxy acids [163,164] .
6.4.5. “ Non - Natural Reaction Types ” in C - C Bond Formation
A very exciting issue in enzyme chemistry is their use for so-called non-natural reactions.
These phenomena, also known as enzyme promiscuity [165], allow interesting organic
synthesis with enzymes, which are known to catalyze other types of reactions in nature.
Notably, a broad range of such “non-natural reaction types” with enzymes as catalysts
are known in the fi eld of C-C bond formations.
Very recently, the Griengl group reported the fi rst enzymatic nitroaldol reaction, also
widely known as Henry reaction [166,167]. An (
S
) - oxynitrilase from
H. brasiliensis
,
which is a highly effi cient biocatalyst for asymmetric hydrocyanation, served as biocata-
lyst, and nitromethane and nitroethane were used as aldol donors. With nitromethane
as donor, a broad range of nitroaldol adducts were obtained with yields up to 77%, and
with enantioselectivities of up to 92% ee. In Scheme 6.45, an example is shown. When
using nitroethane as donor and aldehydes as acceptors, two stereogenic centers are
formed in a diastereo- and enantioselective biotransformation (with a diastereomeric
ratio of d.r. = 90:10 and an enantioselectivity of up to 95% ee).
O
OH
(
S
)-oxynitrilase from
Hevea brasiliensis
NO
2
H
+
Me
NO
2
Buffer-
methyl-
ter t
-butyl ether
(1:1),
pH 7.0, rt
114
91
(
S
)-
115
63% yield
92% ee
Scheme 6.45.
Interestingly, lipases also turned out to be suitable catalysts for Michael reactions. In
the presence of lipases from
C. antarctica
B (CAL-B), several heteroatom nucleophile
donors (such as amines and thiols) were tolerated as well as malonates [168]. However,
the reaction does not proceed enantioselectively (which is in contrast to an early con-
tribution from Kitazume et al. with several amine donors and other hydrolases; see
Reference 169 ).
