Chemistry Reference
In-Depth Information
Kinetic resolution via enzymatic acylation (Route 1):
O
R
4
XH
X
XH
O
Enzyme
rac
R
4
+
+
R
3
OH
+
R
1
R
2
OR
3
R
1
R
2
R
1
R
2
(X=O,NH)
Dynamic kinetic resolution via enzymatic acylation and chemocatalytic racemization (Route 2):
O
R
4
X
XH
O
Enzyme
rac
R
4
+
R
3
OH
+
R
1
R
2
OR
3
R
1
R
2
Racemization
catalyst
(X=O,NH)
Kinetic resolution via transesterification or aminolysis (Route 3):
R
2
R
2
R
2
Enzyme
rac
OR
3
OR
3
R
4
R
4
X
R
3
OH
+
XH
+
+
R
1
R
1
R
1
O
O
O
(X=O,NH)
Scheme 6.2.
solvents and can be used in organic media. Besides two-phase media, lipases can be used
even in pure organic media, which makes them easily compatible with “typical” organic
transformations. Further reasons for lipases' attractiveness are their easy and cheap
access since these enzymes often originate from applications in other (bulk product)
sectors such as detergents and food enzymes. In synthetic applications, lipases turned
out to be highly enantioselective and productive catalysts for enantioselective acylation
of both alcohols and amines. When using a racemic alcohol, lipases generate enantiose-
lectively the acyl form of the preferred enantiomer while leaving the undesired enantio-
mer untouched (Scheme 6.2, Route 1, X= O). While this reaction represents a “ classic ”
enzymatic resolution, combination of a lipase with a chemocatalyst for racemization of
the alcohols enables a dynamic kinetic resolution under (theoretically) quantitative
formation of acylated alcohol (Route 2, X=O) [4]. Replacing the alcohol substrate with
a racemic amine component (Route 1 and 2: X=NH) allows the analogous syntheses of
enantiomerically pure amines. An alternative option is the use of achiral alcohols and
racemic acid components (e.g., esters). The resulting lipase resolution is a so-called
transesterifi cation reaction, which can be useful for the resolution of acid or derivatives
thereof (Route 3, X=O). When carrying out the same reactions with achiral amines
instead of alcohols, the resulting synthesis is a so-called aminolysis reaction (Route 3,
X=NH). This reaction can be useful for the resolution of chiral acid or derivatives
thereof as well (see Section 6.2.4 ).
6.2.2. Acylation Using Racemic Alcohols
The resolution of racemic alcohols in the presence of lipases is a widely known technol-
ogy. To review this type of reaction comprehensively would be beyond the scope of this
review [5]. Therefore, in the following, selected examples are given.
