Nucleotide deoxy sugars

Zervosen A, Stein A, Adrian H et al (1996) Combined enzymatic synthesis of nucleotide (deoxy) sugars from sucrose and nucleoside monophosphates. Tetrahedron 52 2395-2404... 

The key intermediates in the biosynthesis of 6-deoxy sugars are the nucleoside 6-deoxyhexosyl-4-ulose diphosphates (7), formed through enzymic reactions catalyzed by NDP-sugar 4,6-dehydratases (EC 4.2.1.45-47) from primary glycosyl nucleotides. These reactions were observed... 

As shown in the biosynthesis of granaticin, a hydride shift occurs intramolecularly. This process is mediated by an enzyme-bond pyridine nucleotide. A concerted abstraction of H-4 as a hydride in la and a C-5 deprotonation in 2a leads to the 4,5-enol ether 3a. The reduced form of the pyridine nucleotide transfers the hydride to C-6, simultaneously releasing a hydroxide to give 4a. Final tautomerization yields the dTDP-4-keto-6-deoxy-sugar in v-xylo configuration 4a. In other enzymes of the oxidoreductase type, the active site may show a different configuration. Thus, the intermediate 3a can be protonated from above at C-5 to yield the l-arabino isomer of 4a [2]. The stereochemistry of this mechanism was demonstrated by double labelling (cf. l-4b series), and as a net result proved a suprafacial 4—>6 hydride shift. 

The donors of the 6-deoxy sugars are biosynthesised from the nucleotide diphospho derivatives of common sugars, GDP-l-Fuc from GDP-o-Man and dTDP-L-Rha from dTDP-o-Glc (Figure 6.76). Hexoses deoxygenated at... 

Figure 6.76 Pathways for the biosynthesis of nucleotide diphospho sugars of common, 6-deoxy sugars.

Deoxy sugars may be formed by direct reduction at the level of nucleotides by pyridine nucleotide-dependent... 

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. 

Epimerization at C-5 of hexuronic acids is a reaction that proceeds both on the polymer and on the sugar nucleotide level. In addition to the three pairs of parent acids, namely, the u-glucolL-ido-, D manno/L-gulo-, and D-ga-lacto/L-altro-he uron c acids, the 2-amino-2-deoxy acids belonging to the last two and the 2,3-diamino-2,3-dideoxy acids belonging to the middle pair have been found. 

The biosynthesis of Kdo and neuraminic acid is known to involve enol-pyruvate phosphate and D-arabinose or 2-acetamido-2-deoxy-D-mannose, respectively. Nothing is known about the biosynthesis of all the other glycu-losonic acids. One interesting problem is, for example, whether the two 5,7-diamino-3,5,7,9-tetradeoxynonulosonic acids are synthesized analogously to neuraminic acid, from a three- and a six-carbon fragment, by modification of neuraminic acid on the sugar nucleotide level, or by a third, less obvious route. 

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