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182 8 Racemizable Acyl Donors for Enzymatic Dynamic Kinetic Resolution

in the way of the process development. This is the reason why it is so important
to understand under which conditions and by which mechanism a potential acyl
donor is racemized.

8.2.2
The Racemization of Acyl Compounds

In 1997, Zwanenburg and collaborators [31] wrote a comprehensive review about
the controlled racemization of optically active organic compounds. Screening the
literature, they were able, on the one hand, to identify nine classes of substrates
and, on the other hand, to classify the racemization methods that, incidentally,
were also arranged in nine classes.
The Table 8.2 copies an excerpt from this paper to summarize the number of
references concerning the racemization of acyl compounds.
α-Amino acids (and their derivatives) are by far the most studied class, accounting
for more than half of the references. Moreover, for the most employed methodolo-
gies, which are responsible for about 80% of the cases, the epimerization of these
substrates relies on base catalysis, enzyme catalysis, or Schiff base intermediates.
All these mechanisms depend on a reversible α-proton abstraction. Thus, for a
racemization of acyl compound, it is of primary importance to understand the

Table 8.2 Number of references dealing with racemization, organized for the type of func-
tional group and isomerization mechanism.

Thermal Base-catalyzed Acid-catalyzed Schiff base intermediate Enzyme-catalyzed Redox Nucleophilic substitution meso-Intermediate Photochemical Total

R 2
NH
15 57 25 66 56 4 0 1 0 224
R
R 1 3
O
R 2
8 43 20 0 4 1 0 3 4 83
R 3
R 1
O
R 2
O
2 31 4 0 11 2 0 2 0 52
R
R 1 3
O