Page 466 - Cascade_Biocatalysis_Integrating_Stereoselective_and_Environmentally_Friendly_Reactions

442 19 Chemoenzymatic Multistep One-Pot Processes

H 2 O

Catalase
HCO H CO 2
2
O 2 H O 2
2
L-Amino acid
oxidase Artificial
metalloprotein
(Ir-protein catalyst)
NH 2
+
N CO H
H 2 2 N CO H N CO H N CO H
2
2
2
H
H
L-51 52 D-53 L-53
D-Amino
acid oxidase
H 2 O 2 0.5 O 2

Catalase

H O
2
Scheme 19.18 One-pot synthesis of L-pipecolic acid based on combination of three
oxidoreductase-catalyzed reactions and oxidation with an artificial metalloenzyme.

Subsequent in situ oxidation with a d-amino acid oxidase toward 52 proceeds
enantioselectively under consumption of only the d-amino acid, whereas the l-
enantiomer remains unchanged. Thus, this deracemization process then gives
the desired l-pipecolic acid (L-53) with high enantioselectivity [47]. Since, in addi-
tion, a catalase is used to decompose the formed hydrogen peroxide, the overall
one-pot process consists of a combination of three enzymatic reactions with a
compatible artificial metalloprotein-catalyzed transformation [47]. Certainly, an
advantage of this approach to combine artificial metalloproteins with enzymes
can be seen in the fact that, through incorporation of the artificial metal complex
into a protein structure, one can assume a strongly increased compatibility of
this resulting metal–protein complex with other enzyme components (in com-
parison to ‘‘small molecule’’-type metal complexes, which might inhibit and
deactivate enzymes faster through their interaction with the active sites of the
enzymes).