Hexulosonic acids synthesis

Figure 10.12 Stereoselective synthesis ofthe amino acid portion of nikkomycin antibiotics and hexulosonic acids using KDPGIc aldolase.

Synthesis of New Methyl Esters of 3-Deoxy-D- ry /rro-2-hexulosonic acid (KDG) analogs, inducers of the Expression of Pectinase Genes in Bacteria Erwinia chrysanthemi... 

Synthesis by Way of D-xyZo-5-Hexulosonic Acid ( 5-Keto-D-gluconic... 

The D-<2/ <2 z o-hex-2-ulopyranosonates have been used as building blocks for the synthesis of spiroheterocyclic carbohydrates.276,277 The glycosyl donor, methyl (3,4,5-tri-O-acetyl-/J-D- rafo 0-hex-2-ulopyranosyl)onate bromide (102), obtained from the methyl ester of D-uraftinn-2-hexulosonic acid may be converted into its nitrophenyl a-glycoside, which in turn is reductively cyclized to the spirane 103 (Scheme 8). 

C. Di Nardo and O. Varela, Synthesis of furanose derivatives of 3-deoxy-D-erythro-2-hexulosonic acid and their 3-bromo and 3-deuterio analogs, Carbohydr. Res., 328 (2000) 605-610. 

A yield of 60 to 70% of 3,5 4,6-di-0-ethylidene-L-gulonic acid can be readily obtained by the oxidation of one mole of 1,3 2,4-di-0-ethylidene-D-glucitol in the presence of one mole of alkali.According to a patent by D Addieco, this acid can be oxidized to 3,5 4,6-di-O-ethylidene-D-a 2/io-hexulosonic acid by sodium hypochlorite in the presence of nickelous chloride. After hydrolysis of the acetal groups, this acid can be rearranged to L-ascorbic acid. Thus, this provides, for vitamin C, a synthesis which does not require L-sorbose and does not involve bacterial oxidation. A 33% yield of D-xj/fo-hexulosonic acid is obtained. However, nothing is men-... 

The preparation of KDO by using a large excess of o-arabinose The condensation with L-rhamnose, as an example of the complete, inverted stereoselectivity of the sialic acid aldolase The synthesis of 3-deoxy-D-tfireo-hexulosonic acid The synthesis of 3-deoxy-D-araW o-heptulosonic acid... 

A short review (11 pages, 14 references) on the synthesis and evaluation of mechanism-based inhibitors of Kdo8P synthase has appeared. " A review on the alkaline biocatalysis for the direct biosynthesis of iV-acetyl-D-neuraminic acid (NeuSAc) from iV-acetyl-D-glucosamine has also been written. The syntheses of furanose derivatives of 3-deoxy-D-cryt/iro-2-hexulosonic acid and their 3-bromo and 3-deuterio analogues have been reported. 3-Deoxyoctulosonic acid 16 has been prepared by use of E. coli heptulosonate synthase (Scheme 6). ... 

L-xy/o-Hexulosonic acid has been prepared via oxidation of 3,4 5,6-di-0-iso-propylidene-L-sorbose and the racemic derivative (296) was produced on thermolysis of the ozonide (27) (see Chapter 3). 3-Deoxy-D-uw6i/io-[l- C]heptulosonic acid 7-phosphate has been synthesized by addition of potassium [ C]cyanide to 2-deoxy-D-ara6i o-hexose 6-phosphate, hydrolysis, and selective oxidation of the resulting 3-deoxyheptonic acid 7-phosphates at C-2 with potassium chlorate-vanadium(v) oxide. A one-step synthesis of a mixture of 3-deoxy-D-r/6o- and -D-araWno-heptulosonic acid 7-phosphates is based on a metal-ion-catalysed reaction of o-erythrose 4-phosphate with oxalacetate. ... 

A convenient and high-yielding method for the synthesis of crystalline sodium D-arabinonate involves oxidation of D-glucose with oxygen in alkaline methanol-water mixtures. Conditions have been optimised for the catalytic hydrogenation of D-Jcy/o-5-hexulosonic acid so as to give a 3 1 preponderance of L-idonic acid over D-gluconic acid in a very efficient reaction. ... 

Ramage and co-workers have given full details of their Wittig approach to 2-ulosonic acids (see Vol. 22, p.l61) and have extended this route to the synthesis of 3-deoxy-D-eryt/iro-2-hexulosonic acid (KDG, 30), albeit in low yield in this case.33 A French group have developed two routes to KDG (30) (Scheme 5) involving, respectively, a Wittig synthesis of (28) 4 or P elimination from a gluconolactone derivative to yield (29) 35 the second approach could be modified to make 5- and 6-(2-methyl ethers of (30). 

A formal synthesis of L-[6-3H]ascorbic acid was achieved when D-glucurono-6,3-lactone was reduced to L-[6-3H]gulono-l,4-lactone with sodium borotritide.354 L-Gulono-1,4-lactone has been converted into 1 by several routes (see Section III,7b,c). Starting with methyl o-xylo-2-hexulosonate, and following the method shown in Scheme 17, L-(5-2H)ascorbic acid was prepared by reduction of 121 with sodium boro-deuteride.547,548,587 In a related, but shorter, synthesis, sodium D-threo-2,5-hexodiulosonate was reduced with sodium borodeuteride to a mixture of keto-acids (see Section III,9d), which was esterified. By fractional recrystallization, methyl L-xylo-2-hexulosonate was obtained, and this was then converted598 into (5- H)l. 

In a related synthesis methyl D-amfeino-2-hexulosonate (42) was converted, via a series of selectively protected intermediates, into 43, a protected derivative of D-threo-2,5-hexodiulosonic acid (Scheme 23). Stereoselective reduction of 43 with sodium borohydride afforded 44, which was converted to L-ascorbic acid. The overall yield was 36%. This synthesis was also used to prepare l-(5- H) ascorbic acid. 

A fruitful, new extension of catalytic oxidation as a preparative method for special syntheses was established in 1935 when, in conjunction with experiments on the synthesis of L-ascorbic acid (3), Heyns found that selective oxidation of the various hydroxyl functions of carbohydrates was possible. It was shown that the primary hydroxyl group on C-1 of the pyranose form of L-sorbose (1) could be converted to the carboxyl group, giving a 65% yield of L-ajj/Zo-hexulosonic ( 2-keto-L-gulonic ) acid (2). (In formulas (1) and (2), the a-L anomer is depicted.)... 

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