Unfortunately, less than 10% of organic compounds crystallize as a conglomerate (the remainder form racemic crystals) largely denying the possibility of separating enantiomers by simple crystallization techniques – such as by seeding a
supersaturated solution of the racemate with crystals of one pure enantiomer.
Previously, enantiomerically pure auxiliary reagents were used in catalytic or in
stoichiometric amounts [90]. They are often expensive and cannot always be
recovered. Likewise, starting a synthesis with an enantiomerically pure compound
from the stock of enantiopure natural compounds [91] such as carbohydrates, amino
acids, terpenes or steroids – the so-called ‘chiral pool’ – has its limitations
[92]. Considering the above-mentioned problems, it is obvious that enzymatic
methods represent a valuable addition to the existing toolbox available for the
asymmetric synthesis of fine chemicals [93].
1.3.2 Disadvantages of Biocatalysts
There are certainly some drawbacks worthy of mention for a chemist intent on
using biocatalysts:
• Enzymes are provided by nature in only one enantiomeric form.
Since there is no natural way of creating mirror-image enzymes from D-amino
acids, it is impossible to invert the chiral induction of a given enzymatic reaction
by choosing the ‘other enantiomer’ of the biocatalyst, a strategy which is
possible with chiral chemical catalysts. To gain access to the other enantiomeric
product, one has to follow a long and uncertain path in search for an enzyme with
exactly the opposite stereochemical selectivity. However, this is sometimes
possible, and strategies how nature transforms mirror-image substrates using
stereo-complementary enzymes have recently been analyzed [94].
• Enzymes require narrow operation parameters.
The obvious advantage of working under mild reaction conditions can sometimes turn into a drawback. If a reaction proceeds too slow under given parameters
of temperature or pH, there is only a narrow operational window for alteration.
Elevated temperatures as well as extreme pH lead to deactivation of the protein, as
do high salt concentrations. The usual technique to increase selectivity by lowering the reaction temperature is of limited use with enzymatic transformations,
although some enzymes remain catalytically active even in ice [95, 96]. Hence,
the narrow temperature range for the operation of enzymes prevents radical
changes, although positive effects from small changes have been reported [97].
• Enzymes display their highest catalytic activity in water.
Due to its high boiling point, high heat of vaporization and its tendency to
promote corrosion, water is usually the least suitable solvent for most organic
reactions, although it is the ‘greenest’ of all solvents [98]. Furthermore, the
1.3 Advantages and Disadvantages of Biocatalysts
7
supersaturated solution of the racemate with crystals of one pure enantiomer.
Previously, enantiomerically pure auxiliary reagents were used in catalytic or in
stoichiometric amounts [90]. They are often expensive and cannot always be
recovered. Likewise, starting a synthesis with an enantiomerically pure compound
from the stock of enantiopure natural compounds [91] such as carbohydrates, amino
acids, terpenes or steroids – the so-called ‘chiral pool’ – has its limitations
[92]. Considering the above-mentioned problems, it is obvious that enzymatic
methods represent a valuable addition to the existing toolbox available for the
asymmetric synthesis of fine chemicals [93].
1.3.2 Disadvantages of Biocatalysts
There are certainly some drawbacks worthy of mention for a chemist intent on
using biocatalysts:
• Enzymes are provided by nature in only one enantiomeric form.
Since there is no natural way of creating mirror-image enzymes from D-amino
acids, it is impossible to invert the chiral induction of a given enzymatic reaction
by choosing the ‘other enantiomer’ of the biocatalyst, a strategy which is
possible with chiral chemical catalysts. To gain access to the other enantiomeric
product, one has to follow a long and uncertain path in search for an enzyme with
exactly the opposite stereochemical selectivity. However, this is sometimes
possible, and strategies how nature transforms mirror-image substrates using
stereo-complementary enzymes have recently been analyzed [94].
• Enzymes require narrow operation parameters.
The obvious advantage of working under mild reaction conditions can sometimes turn into a drawback. If a reaction proceeds too slow under given parameters
of temperature or pH, there is only a narrow operational window for alteration.
Elevated temperatures as well as extreme pH lead to deactivation of the protein, as
do high salt concentrations. The usual technique to increase selectivity by lowering the reaction temperature is of limited use with enzymatic transformations,
although some enzymes remain catalytically active even in ice [95, 96]. Hence,
the narrow temperature range for the operation of enzymes prevents radical
changes, although positive effects from small changes have been reported [97].
• Enzymes display their highest catalytic activity in water.
Due to its high boiling point, high heat of vaporization and its tendency to
promote corrosion, water is usually the least suitable solvent for most organic
reactions, although it is the ‘greenest’ of all solvents [98]. Furthermore, the
1.3 Advantages and Disadvantages of Biocatalysts
7