DTDP-deoxy sugars synthesis

With 2-deoxy-D-glucose-6-phosphate 6 as starting substrate and an additional enzymatic step the synthesis of dTDP-2,6 dideoxy-4-ketoglucose 7, an important intermediate of dTDP-deoxy sugars, and dTDP-P-L-olivose 8 was realized (Scheme 5.2) [68]. 

Figure 6.2 Sequential cascade reaction for the synthesis of dTDP-deoxy sugars, (a) dTMP-kinase, (b) pyruvate kinase, (c) sucrose synthase (SuSy), (d) dTDP-GIc 4,5-dehydratase (RmlB), (e) 3,5-epimerase (RmIC or DnmU), (f) 4-keto reductase (RmID), and (g) formate dehydrogenase [82].

Starting from sucrose, one-pot reactions are suitable to work as regeneration cycles for nucleotide sugars as demonstrated for UDP-Glc, UDP-Gal, and dTDP-deoxy-sugars [98-103] (Scheme 6.4). Sucrose synthase (SuSy), known for the reverse reaction of a GT, is used in combination with different enzyme module systems. Nucleoside diphosphate (NDP) from GT modules are substrates of SuSy catalyzed synthesis of activated glucose (UDP-Glc, dTDP-Glc) which enter enzyme modules to generate the donor substrates of GTs. 

Rupprath, C., Kopp, M., Hirtz, D. et al. (2007) An enzyme module system for in situ regeneration of deoxythymidine 5 -diphosphate (dTDP)-activated deoxy sugars. Advanced Synthesis Catalysis, 349, 1489-1496. 

Recently, some knowledge was acquired concerning nature s approach to the synthesis of dideoxy sugars. 6-Deoxygenation of glucose seems to follow a redox pathway via the nucleotide glucoside dTDP-glucose with oxidoreductase which leads to a 6-deoxy-4-uloside [1],... 

One-pot synthesis of nucleotide sugars was also demonstrated for multi-enzyme systems as shown for UDP-Gal [107, 108] and dTDP-2-deoxy-Glc [109]. Even some modified sugar nucleotides were synthesized in an one-pot fashion, namely UDP-carba-sugars based on Gal, GlcNAc, Glc, and Man [110]. The cascade involved uridine monophosphate (UMP)-kinase and acetate kinase to generate uridine triphosphate (UTP) as well as Glc-l-P-uridyltransferase, Gal-l-P-uridyltransferase,... 

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