• Many oxidants are based on metal ions such as copper, manganese, iron, nickel,
or chromium, which are often environmentally incompatible when used on large
scale.
• Undesired side reactions are common due to a lack of chemoselective oxidation
methods.
• The most inexpensive and innocuous oxidant, molecular oxygen, cannot be used
efficiently.
• It is extremely difficult to perform oxidations in a regio- and stereoselective
fashion.
Therefore, organohalogens have been widely used as intermediates for the
synthesis of oxygenated compounds, which has led to severe environmental problems due to recalcitrant halogenated organic compounds.
Many of the drawbacks mentioned above can be circumvented by using biological oxidation, in particular for those cases where stereoselectivity is required
[1143–1145].
The biooxidation reactions discussed in this chapter are grouped according to
their requirement for the oxidant, i.e.:
• Dehydrogenation depending on a nicotinamide cofactor [NAD(P)H] (Sect.
2.3.1)
• Oxidation and oxygenation at the expense of molecular oxygen (Sect. 2.3.1,
2.3.2 and 2.3.3)
• Peroxidation reactions requiring hydrogen peroxide or a derivative thereof (Sect.
2.3.4)
For a classification of biooxidation reactions see Scheme 2.144.
2.3.1 Oxidation of Alcohols and Aldehydes
Oxidations of primary and secondary alcohols to furnish aldehydes and ketones,
respectively, are common chemical reactions that rarely present insurmountable
problems to the synthetic organic chemist. These reactions can be catalysed by
alcohol dehydrogenases together with NAD(P)
+ -recycling. However, in contrast to
the corresponding (carbonyl) reduction reactions, alcohol oxidation using dehydrogenases have been reported to a lesser extent for the following reasons [1146]:
• Oxidations of alcohols using NAD(P)
+
-dependent dehydrogenases are thermodynamically unfavorable. Thus, the recycling of the oxidized nicotinamide
cofactor becomes a complicated issue (see Scheme 2.111).
• Enzymatic oxidations usually work best at elevated pH (8–9) where nicotinamide cofactors and (particularly aldehydic) products are unstable.
• Lipophilic aldehydes or ketones are often more tightly bound onto the hydrophobic active site of dehydrogenases than the more hydrophilic substrate alcohol. Hence, product inhibition is a common phenomenon, in particular when
reactive aldehydes are involved [846].
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2 Biocatalytic Applications
or chromium, which are often environmentally incompatible when used on large
scale.
• Undesired side reactions are common due to a lack of chemoselective oxidation
methods.
• The most inexpensive and innocuous oxidant, molecular oxygen, cannot be used
efficiently.
• It is extremely difficult to perform oxidations in a regio- and stereoselective
fashion.
Therefore, organohalogens have been widely used as intermediates for the
synthesis of oxygenated compounds, which has led to severe environmental problems due to recalcitrant halogenated organic compounds.
Many of the drawbacks mentioned above can be circumvented by using biological oxidation, in particular for those cases where stereoselectivity is required
[1143–1145].
The biooxidation reactions discussed in this chapter are grouped according to
their requirement for the oxidant, i.e.:
• Dehydrogenation depending on a nicotinamide cofactor [NAD(P)H] (Sect.
2.3.1)
• Oxidation and oxygenation at the expense of molecular oxygen (Sect. 2.3.1,
2.3.2 and 2.3.3)
• Peroxidation reactions requiring hydrogen peroxide or a derivative thereof (Sect.
2.3.4)
For a classification of biooxidation reactions see Scheme 2.144.
2.3.1 Oxidation of Alcohols and Aldehydes
Oxidations of primary and secondary alcohols to furnish aldehydes and ketones,
respectively, are common chemical reactions that rarely present insurmountable
problems to the synthetic organic chemist. These reactions can be catalysed by
alcohol dehydrogenases together with NAD(P)
+ -recycling. However, in contrast to
the corresponding (carbonyl) reduction reactions, alcohol oxidation using dehydrogenases have been reported to a lesser extent for the following reasons [1146]:
• Oxidations of alcohols using NAD(P)
+
-dependent dehydrogenases are thermodynamically unfavorable. Thus, the recycling of the oxidized nicotinamide
cofactor becomes a complicated issue (see Scheme 2.111).
• Enzymatic oxidations usually work best at elevated pH (8–9) where nicotinamide cofactors and (particularly aldehydic) products are unstable.
• Lipophilic aldehydes or ketones are often more tightly bound onto the hydrophobic active site of dehydrogenases than the more hydrophilic substrate alcohol. Hence, product inhibition is a common phenomenon, in particular when
reactive aldehydes are involved [846].
168
2 Biocatalytic Applications