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19.3 Combination of Substrate Isomerization and their Derivatization 429

synthesis, the biotransformation can be integrated as an initial or a subsequent step
depending on the desired product and reaction sequence. Enzyme compatibility
with the reaction mixture of the chemocatalytic or chemical process becomes a
critical issue only when using the biotransformation as a second step. Notably,
in spite of this challenge in recent years several such one-pot processes have
successfully been developed.
In the following, we give an overview on the research developments referring
to both types of concepts, that is, concept (a) or concept (b). Although this review
will also describe key historical developments in the field, the major focus will
be on more recently developed synthetic examples. Thus, this review should be
considered as an extension of previous overviews on chemoenzymatic syntheses
described earlier with a different focus by, for example, Kieboom et al. [3], Faber
et al. [4], B¨ ackvall et al. [5, 6], and Pellisier [7].

19.3
Combination of Substrate Isomerization and their Derivatization with Chemo- and
Biocatalysts Resulting in Dynamic Kinetic Resolutions and Related Processes
Notably, the first process concept in this area of combining chemo- and biocatal-
ysis in a one-pot process was reported by the van Bekkum group in 1980 [8],
demonstrating a successful combination of an enzymatic isomerization with a
heterogeneous catalytic hydrogenation reaction. In detail, a d-glucose isomerase
catalyzes the isomerization of d-glucose into d-fructose, while a preferential in situ
platinum-catalyzed hydrogenation of d-fructose (compared with d-glucose) gives
an enhanced amount of the desired sugar substitute d-mannitol (Scheme 19.2).
When using the enzyme in the immobilized form (in gelatin and cross-linked

CHO CH OH
2
H OH D-Glucose O
HO H isomerase HO H
R R
D-Glucose (D-1) D-Fructose (D-2)
Heterogeneous
metal catalyst, R:
H 2
H OH
H OH
CH OH
2
OH CH OH
CH 2 2
H OH HO H
HO H HO H
R R
D-Glucitol (D-3) D-Mannitol (D-4)

Scheme 19.2 One-pot synthesis of D-mannitol based on combination of enzymatic isomer-
ization of D-glucose and heterogeneous hydrogenation.