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140 6 Chemo-Enzymatic Cascade Reactions for the Synthesis of Glycoconjugates

2−
OPO 3
O
HO
HO
OH
dTTP
a
2P
PP i i
OH
O
HO
HO
OdTDP
b

O Me
O
HO
OdTDP
c d
HO
Me Me
Me O O O
HO OdTDP HO HO or HO
HO
OdTDP OdTDP

Figure 6.1 Sequential cascade reaction for the synthesis of dTDP-2,6-dideoxyhexoses. (a)
Phosphoglucomutase, dTDP-Glc pyrophosphorylase (RmlA), pyrophosphatase, (b) dTDP-Glc
4,6-dehydratase (RmlB), (c) 3,5-epimerase (RmlC), 4-keto reductase (RmlD), and (d) NaBH 4
[81].

(SuSy) and thymidine monophosphate kinase (dTMP)-kinase for the formation of
dTDP-Glc from dTMP and sucrose followed by the action of RmlB to yield dTDP-
4-keto-6-deoxy-Glc (Figure 6.2) [82]. After 3,5-epimerization of the intermediate
with RmlC or DnmU, the final enzymatic step using RmlD yielded dTDP-β-
l-rhamnose. Furthermore, the intermediate product dTDP-4-keto-6-deoxyglucose
could be chemically reduced to dTDP-d-quinovose and dTDP-d-fucose. Within
each enzymatic part, the valuable nucleotides and co-factors were regenerated in
situ enzymatically.
Unnatural nucleotide sugars are interesting compounds as novel substrates
for GTs in tasks like glycan-specific nonradioactive labeling. Biotin-derivatives of
UDP-Gal/-GalNAc derivatives were synthesized with a chemo-enzymatic cascade
reaction (Figure 6.3) [83, 84].
Starting from UDP-Glc/UDP-GlcNAc biocatalytic epimerization and oxidation
were combined with chemical hydrazone formation. These simultaneously occur-
ring steps may be also classified as chemo-enzymatic one-pot cascade reaction.