secondary alcohols - deracemization - domino reaction - oxidation
Significance
<P>Biocatalytic deracemization of
sec-alcohols
rac-
1 has been achieved through a concurrent stereoselective oxidation-reduction sequence
affording the
S-enantiomer
S-
1 in highly enantioenriched form (up to er > 99.5:0.5). The authors have identified
resting cells of
Alcaligenes faecalis DSM 13975 as a highly active and
R-enantioselective catalyst for the oxidation of
sec-alcohols. Molecular oxygen serves as oxidant. In the reduction step, an
S-selective alcohol dehydrogenase, either ADH-‘A’ or RE-ADH, in combination with a
cofactor recycling system (glucose/ GDH) was effective. The method has also been applied
to the stereoinversion of an enantiopure
sec-alcohol. A related system gives access to the
R-enantiomer through
S-enantioselective oxidation and
R-stereoselective reduction.</P>
Comment
<P>Dynamic kinetic resolution of
sec-alcohols through the racemization of the alcohol moiety in combination with an (enzymatic)
kinetic resolution is a well-established strategy. For the deracemization of alcohols
through enantioselective oxidation and simultaneous stereoselective reduction of
the corresponding ketones no general protocol has been described due to the lack of
an applicable
sec-alcohol oxidase. In the present work, two examples highlight the use of 2-propanol
as an alternative cofactor recycling system resulting in only slightly reduced enantioselectivities.
Both enantiomeric forms of the
sec-alcohol are accessible. The
R-enantiomer, however, is obtained with generally lower enantioselectivities.</P>
