Hexulosonic acids preparation

The most important oxidation product of L-gulono-1,4-lactone (I) is, without a doubt, L-ascorbic acid (6 vitamin C), and the most important oxidation product of L-gulonic acid (3) is L-xyZo-2-hexulosonic acid (5), which serves as a key intermediate in the commercial production of L-ascorbic acid. The literature covering the methods by which 1 or 3 (or derivatives thereof) has been converted into 6 or 5, as well as other methods for the preparation of 6, has been reviewed,1 and will not be discussed here. 

An alternative procedure for the protection of L-sorbose (25), followed by oxidation at C-l and cyclization of the product to L-ascorbic acid, was developed by Hinkley and Hoinowski.257 L-Sorbose (25) was converted into methyl a-L-sorbopyranoside (37) by treatment with methanol and hydrogen chloride.258 Glycoside 37 was then oxidized with air in the presence of a suspension of platinum oxide in aqueous sodium hydrogencarbonate solution at 60°, to afford methyl ot-L-xylo-2-hexulopyranosidonic acid (38), which, when heated in hydrochloric acid, was converted into L-ascorbic acid (1), presumably by way of L-xy/o-2-hexulosonic acid (see Scheme 5). Acid 38 has also been prepared by oxidation of 37 with nitrogen tetraoxide.259,280 Yields were not reported for this reaction sequence, and it appears to offer no potential... 

As stated in Section III,6, L-ascorbic acid may be prepared by converting L-glucose (8) into D-glucuronic acid (54), followed by reduction of 54 to L-gulonic acid (47), which can then be converted into L-xylo-2-hexulosonic acid (28) (or its equivalent), and this into 1. In the present Section, the methods by which L-gulonic acid (47) has been prepared will be presented, followed by a discussion of the methods by which it has been converted into 28 and 1. 

The enzyme system in A. melanogenum that is responsible for the oxidation of D-arafomo-2-hexulosonic acid (48) to 96 has been separated and partially purified.517 It was discovered518-520 that 96 is further oxidized to carbon dioxide and 2-oxopentanedioic acid (a-ketoglutaric acid) (102) when phenazine methosulfate is added to a cell-free enzyme-preparation from A. melanogenum. 

A number of papers describe the preparation of glyculosonic acids by bacteria. The genus Pseudomonas is reported to be particularly efficient for the preparation of D-araZh o-2-hexulosonic acid (94), a compound used on the industrial scale for production of isoascorbic acid. Lockwood described the preparation of 94 in good yield by such a strain.279 2-Glyculosonic acids can be degraded to lower aldonic acids by the Ruff procedure. 

Raney nickel) of the potassium salt of D-xy/o-5-hexulosonic acid oxime produces a mixture of 5-amino-5-deoxy-L-idonic and -D-glu-conic acid in the ratio of 2 1, which is converted into the methyl ester hydrochloride. Upon treatment with alkali, spontaneous cyclization to the pair of 1,5-lactams occurs. 5-Amino-5-deoxy-L-idono-l,5-lactam and 5-amino-5-deoxy-D-glucono-l,5-lactam were separated by recrystallization. The optical rotatory dispersion curves of both compounds were discussed. A new type of lactam, namely, 2-enamino-N,N -bis[(p-methoxycarbonyl)phenyl]-4-(D-gaiacfo-penta-acetoxypentyl)-4-butanelactam was prepared by tbe reaction of 5,6,7,8,9-penta-0-acetyl-3,4-dideoxy-D-ga/ocfo-nonulos- rcns-3-en-l-onic acid with methyl p-aminobenzoate. 

Blocked L-sorbose derivatives can be catalytically oxidized in high yields to the corresponding L-xyZo-hexulosonic acid derivatives, using platinum-on-carbon. From the catalytic oxidation of 2,3 4,6-di-0-isopropylidene-L-sorbose, an almost quantitative jdeld of 2,3 4,6-di-0-isopropylidene-L-a /lo-hexulosonic acid has been reported. Similarly, methyl a-L-sorboside gives a quantitative yield of methyl a-L-xylo-hexulosidonic acid. Attempts to prepare L-xylo-hexulosonic acid from this product result in extensive... 

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). ... 

A specially prepared palladium on charcoal catalyst permits the oxidation of L-sorbose to L-xyto-hexulosonic acid in 50 % yield and is of potential value in the industrial production of vitamin C. The inhibitory effect of various... 

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. ... 

The preferred method of preparing 74 for laboratory use is by the dehydration of D-xt/lo-5-hexulosonic ( 5-keto-D-gluconic ) acid in refluxing, 5% methanolic hydrogen chloride the crystalline, methyl ester of 74 can then be isolated in 17.4% yield.110 Crystalline 74 is readily prepared from the methyl ester by saponification. Pure 74 has m.p. 200-201° and kmaX = 286 nm (e = 18,000) in water. 

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.)... 

Aldulosonic acids can also be prepared by the electro-oxidation of aldosuloses ( osones ) in buffered solutions containing calcium carbonate and bromide further oxidation of the products obtained may occur. Calcium n-archtno-hexulosonate (6) yields calcium D-arabinonate (7) on... 

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