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8
Racemizable Acyl Donors for Enzymatic Dynamic Kinetic
Resolution

Davide Tessaro

8.1
Introduction

As noted by Faber [1], about two-thirds of the total research in the biocatalysis field
has been carried out using hydrolytic enzymes, probably because of their large
availability, their ease of use (also owing to their lack of special cofactors), and their
variety in terms of substrate specificity and stereo preference.
Hydrolases are often applied in the production of enantiopure substances through
the so-called kinetic resolution (KR): when reacting on a racemate, the catalyst acts
preferentially on one of the two enantiomers, leaving the other one untouched;
if the enzyme’s enantioselectivity is high enough, this permits the separation of
the two enantioforms. Nevertheless, it is well known that a major drawback of a
KR is the 50% of maximum yield on the single enantiomer, which, especially for
industrial applications, greatly limits its utility. The unwanted enantiomer, in fact,
has to be separated and, if possible, racemized again in order to be recycled for a
successive batch.
A huge improvement on the KR is determined by an enhanced reaction setup
where the racemization of the substrate is carried out in situ in parallel to its
resolution. This means that, while the preferred enantiomer is transformed by
the enzyme, the other one does not accumulate but is continuously converted
into its antipode, thus fueling the reaction until all the substrate is consumed. In
this case, a quantitative conversion can be reached; moreover, the enantiomeric
purity of the product is often higher as compared to the simple KR, because
the enzyme is continuously exposed to comparable concentrations of both of the
two stereoisomers, which is a requirement for the maximum efficiency in their
discrimination [2, 3]. This improved setup is called dynamic kinetic resolution (DKR),
and it has become very attractive in recent years [4–9].
An efficient DKR is based on three requirements: (i) the enzyme must be highly
stereoselective, (ii) the racemization of the substrate should be at least as fast as
the successive transformation of its reactive enantiomer, (iii) the product must not
racemize under the reaction conditions. Hence, out of the three conditions, two
deal with the racemization rates. It is not surprising, then, that from this perspective

Cascade Biocatalysis: Integrating Stereoselective and Environmentally Friendly Reactions, First Edition.
Edited by Sergio Riva and Wolf-Dieter Fessner.
c 2014 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2014 by Wiley-VCH Verlag GmbH & Co. KGaA.