• An incoming amine R
3 –NH 2 results in the formation of an N-substituted amide
R
1 –CO–NH–R
3 , yielding an enzymatic aminolysis of esters [17, 18].
• Hydrazinolysis provides access to hydrazides [19, 20], and the action of hydroxylamine results in the formation of hydroxamic acid derivatives [21].
• Peracids of type R
1 –CO–OOH are formed when hydrogen peroxide is acting as
the nucleophile [22].
• Thiols (which would lead to thioesters) are unreactive [23].
During the course of all of these reactions, any type of chirality in the substrate is
‘recognized’ by the enzyme, which causes a preference for one of the two possible
stereochemical pathways. The magnitude of this discrimination is governed by the
kinetics and is a crucial parameter since it stands for the ‘selectivity’ of the reaction.
It should be noted, that the following chapter is not an elaboration on enzyme
kinetics, but rather a compilation of the most important conclusions needed for
obtaining optimal results from stereoselective enzymatic transformations.
Since hydrolases nicely exemplify all different types of chiral recognition, we
will discuss the underlying principles of these chiral recognition processes and the
corresponding kinetic implications here [24]. Most of these types of transformations can be found within other groups of enzymes as well, and the corresponding
rules can be applied accordingly.
Enantioface Differentiation
Hydrolases can distinguish between the two enantiomeric faces of achiral substrates
such as enol esters possessing a plane of symmetry within the molecule [25]. The attack
of the enzyme’s nucleophilic chemical operator predominantly occurs from one side,
leading to an unsymmetric enolization of the unstable free enol towards one preferred
side within the chiral environment of the enzyme’s active site [26]. During the course
of the reaction a new center of chirality is created in the product (Scheme 2.2).
Z
O
-
Y
X
R
O
Z
O
Y
X
O
CH 2 Ar
O
O
O
O
O
O
O CH 2 Ar
O
O
O
O CH 2 Ar
O
Y
X
H
O
Z
k 1
Hydrolase
a sequence rule order of
X > Y > Z is assumed
chiral product
*
*
k 2
si
re
achiral precursor with
plane of symmetry
*
Ar = aryl
R
S
Scheme 2.2 Enantioface differentiation (achiral substrates)
2.1 Hydrolytic Reactions
33
3 –NH 2 results in the formation of an N-substituted amide
R
1 –CO–NH–R
3 , yielding an enzymatic aminolysis of esters [17, 18].
• Hydrazinolysis provides access to hydrazides [19, 20], and the action of hydroxylamine results in the formation of hydroxamic acid derivatives [21].
• Peracids of type R
1 –CO–OOH are formed when hydrogen peroxide is acting as
the nucleophile [22].
• Thiols (which would lead to thioesters) are unreactive [23].
During the course of all of these reactions, any type of chirality in the substrate is
‘recognized’ by the enzyme, which causes a preference for one of the two possible
stereochemical pathways. The magnitude of this discrimination is governed by the
kinetics and is a crucial parameter since it stands for the ‘selectivity’ of the reaction.
It should be noted, that the following chapter is not an elaboration on enzyme
kinetics, but rather a compilation of the most important conclusions needed for
obtaining optimal results from stereoselective enzymatic transformations.
Since hydrolases nicely exemplify all different types of chiral recognition, we
will discuss the underlying principles of these chiral recognition processes and the
corresponding kinetic implications here [24]. Most of these types of transformations can be found within other groups of enzymes as well, and the corresponding
rules can be applied accordingly.
Enantioface Differentiation
Hydrolases can distinguish between the two enantiomeric faces of achiral substrates
such as enol esters possessing a plane of symmetry within the molecule [25]. The attack
of the enzyme’s nucleophilic chemical operator predominantly occurs from one side,
leading to an unsymmetric enolization of the unstable free enol towards one preferred
side within the chiral environment of the enzyme’s active site [26]. During the course
of the reaction a new center of chirality is created in the product (Scheme 2.2).
Z
O
-
Y
X
R
O
Z
O
Y
X
O
CH 2 Ar
O
O
O
O
O
O
O CH 2 Ar
O
O
O
O CH 2 Ar
O
Y
X
H
O
Z
k 1
Hydrolase
a sequence rule order of
X > Y > Z is assumed
chiral product
*
*
k 2
si
re
achiral precursor with
plane of symmetry
*
Ar = aryl
R
S
Scheme 2.2 Enantioface differentiation (achiral substrates)
2.1 Hydrolytic Reactions
33