Some major exceptions, for which equivalent reaction types have not (yet) been
found in nature, is the Cope rearrangement – although [3,3]-sigmatropic rearrangements such as the Claisen rearrangement are known [71, 72]. On the other hand,
some biocatalysts can accomplish reactions extremely difficult to emulate in
organic chemistry, such as the selective functionalization of nonactivated C-H
bond of aliphatics.
Enzymes display three major types of selectivities:
– Chemoselectivity
Usually an enzyme acts on a single type of functional group, leaving other
sensitive functionalities, which would react under chemical catalysis,
unchanged. As a result, reactions generally tend to be ‘cleaner’ so that laborious
removal of impurities arising from side reactions, can largely be omitted.
– Regioselectivity and Diastereoselectivity
Due to their complex three-dimensional structure, enzymes can distinguish
between functional groups which are chemically identical but situated in different positions within the same substrate molecule [73, 74].
– Enantioselectivity
Last but not least, all enzymes are made from L-amino acids and thus are
chiral catalysts.
7 As a consequence, any type of chirality present in the substrate
molecule is ‘recognized’ upon formation of the enzyme-substrate complex.
Thus, a prochiral substrate may be transformed into an optically active product
through a desymmetrization process and both enantiomers of a racemic substrate
usually react at different rates, affording a kinetic resolution. These latter
properties collectively constitute the ‘stereoselectivity’ (in desymmetrizations)
or ‘enantioselectivity’ (in kinetic resolutions) of an enzyme and represent its
most important feature for asymmetric exploitation [76]. It is remarkable that
this key feature was already recognized by E. Fischer back in 1898 [77].
All the major biochemical events taking place within an organism are governed
by enzymes. Since the majority of them are highly selective with respect to the
chirality of a substrate, it is obvious that the enantiomers of a given bioactive
compound such as a pharmaceutical or an agrochemical will cause different
biological effects [78]. Consequently, in a biological context, enantiomers must
be regarded as two distinct species. The isomer with the desired activity is denoted
as the ‘eutomer’,
8 whereas its enantiomeric counterpart, possessing less or even
undesired activities, is termed as the ‘distomer’.
9 The range of effects derived from
the distomer can extend from lower (although positive) activity, no response or
toxic events. The ratio of the activities of both enantiomers is defined as the
‘eudismic ratio’. Some representative examples of different biological effects are
given in Scheme 1.1.
7 For synthetically produced D-chiral proteins see [75].
8 From Ancient Greek ‘ευ’, meaning ‘good’.
9 The Latin prefix ‘dis’ means ‘apart’, or having a negavite or reversing force.
1.3 Advantages and Disadvantages of Biocatalysts
5
found in nature, is the Cope rearrangement – although [3,3]-sigmatropic rearrangements such as the Claisen rearrangement are known [71, 72]. On the other hand,
some biocatalysts can accomplish reactions extremely difficult to emulate in
organic chemistry, such as the selective functionalization of nonactivated C-H
bond of aliphatics.
Enzymes display three major types of selectivities:
– Chemoselectivity
Usually an enzyme acts on a single type of functional group, leaving other
sensitive functionalities, which would react under chemical catalysis,
unchanged. As a result, reactions generally tend to be ‘cleaner’ so that laborious
removal of impurities arising from side reactions, can largely be omitted.
– Regioselectivity and Diastereoselectivity
Due to their complex three-dimensional structure, enzymes can distinguish
between functional groups which are chemically identical but situated in different positions within the same substrate molecule [73, 74].
– Enantioselectivity
Last but not least, all enzymes are made from L-amino acids and thus are
chiral catalysts.
7 As a consequence, any type of chirality present in the substrate
molecule is ‘recognized’ upon formation of the enzyme-substrate complex.
Thus, a prochiral substrate may be transformed into an optically active product
through a desymmetrization process and both enantiomers of a racemic substrate
usually react at different rates, affording a kinetic resolution. These latter
properties collectively constitute the ‘stereoselectivity’ (in desymmetrizations)
or ‘enantioselectivity’ (in kinetic resolutions) of an enzyme and represent its
most important feature for asymmetric exploitation [76]. It is remarkable that
this key feature was already recognized by E. Fischer back in 1898 [77].
All the major biochemical events taking place within an organism are governed
by enzymes. Since the majority of them are highly selective with respect to the
chirality of a substrate, it is obvious that the enantiomers of a given bioactive
compound such as a pharmaceutical or an agrochemical will cause different
biological effects [78]. Consequently, in a biological context, enantiomers must
be regarded as two distinct species. The isomer with the desired activity is denoted
as the ‘eutomer’,
8 whereas its enantiomeric counterpart, possessing less or even
undesired activities, is termed as the ‘distomer’.
9 The range of effects derived from
the distomer can extend from lower (although positive) activity, no response or
toxic events. The ratio of the activities of both enantiomers is defined as the
‘eudismic ratio’. Some representative examples of different biological effects are
given in Scheme 1.1.
7 For synthetically produced D-chiral proteins see [75].
8 From Ancient Greek ‘ευ’, meaning ‘good’.
9 The Latin prefix ‘dis’ means ‘apart’, or having a negavite or reversing force.
1.3 Advantages and Disadvantages of Biocatalysts
5