Sugar 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... 

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. 

The main function of the ester 34 in bacterial cells seems to be its participation in the biosynthesis of the glycopeptide cell-wall polymer. If this process is blocked, there results the accumulation of a high concentration of sugar nucleotide precursors in the cell. A number of these compounds have been isolated the simplest one is the ester of uridine 5 -pyrophosphate with N-acetylmuramic acid [2-acetamido-3-0-(D-l-carboxyethyl)-2-deoxy-D-glucose] (37), first obtained from Staphylococcus aureus cells that had been treated with penicillin7,151 or Gentian Violet.144 An intermediate in the biosynthesis of 37 was isolated and shown to be the 3 -enolpyruvate ether152,153 (38). 

The analog of this sugar nucleotide lacking the hydroxyl group at C-2", namely, uridine 5 -(2-deoxy-a-D-/yxo-hexopyranosyl pyrophosphate) is formed in admixture with uridine 5 -(2-deoxy-a-D-arabino-hexopyranosyl pyrophosphate) when yeasts249 or higher plants250 are treated with 2-deoxy-D-ft/xo-hexopyranose. 

Animal tissues have been reported to contain the pyrophosphor-ylase of uridine 5 -(2-acetamido-2-deoxy-a-D-galactopyranosyl pyrophosphate),253 which may be used for the synthesis of this sugar nucleotide it has also been prepared254 according to Scheme 6,... 

Unlike the examples previously discussed, this interaction leads to splitting of the pyrophosphate linkage in the sugar nucleotide, with the liberation of nucleoside 5 -phosphate. Such reactions have been demonstrated for a-D-galactopyranosyl,468-488 2-acetamido-2-deoxy-a-D-glucopyranosyl,335,470 and pentapeptidyl-muramyl471,472 esters of uridine 5 -pyrophosphate. 

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... 

FIGURE 24.15 General structures of (a) a nucleoside and (b) a nucleotide. When Y = H, the sugar is deoxy-ribose when Y = OH, the sugar is ribose. 

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. 

Epimerization at C-2 of a sugar nucleotide has been described. An enzyme from Escherichia coli catalyzes the epimerization of UDP-2-acetamido-2-deoxy-D-glucose to UDP-2-acetamido-2-deoxy-D-mannose.59 Such an epimerization, together with the 3,5-epimerase reaction of a 4-ketose and stereospecific reduction at C-4, could lead to inversion at all of the chiral centers of, for instance, 2-amino-2-deoxy-D-glucose. 

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