Oxidation L-ascorbic acid

Calcium oxalate monohydrate Sodium formate oxalic acid source Potassium oxalate oxidant, food L-Ascorbic acid oxidant, rocket fuels Perchloryl fluoride oxidant, selective... 

Bergner, K. G. 1947. The behavior of L-ascorbic acid-oxidizing enzymes and copper ions toward sulfur dioxide. Deut. Lebensm.-Rundschau 43, 95 C. A. 44, 7363 (1950). 

The most significant chemical characteristic of L-ascorbic acid (1) is its oxidation to dehydro-L-ascorbic acid (L-// fi (9-2,3-hexodiulosonic acid y-lactone) (3) (Fig. 1). Vitamin C is a redox system containing at least three substances L-ascorbic acid, monodehydro-L-ascorbic acid, and dehydro-L-ascorbic acid. Dehydro-L-ascorbic acid and the intermediate product of the oxidation, the monodehydro-L-ascorbic acid free radical (2), have antiscorbutic activity equal to L-ascorbic acid. 

The reversible oxidation of L-ascorbic acid to dehydro-L-ascorbic acid is the basis for its known physiological activities, stabiUties, and technical apphcations (2). The importance of vitamin C in nutrition and the maintenance of good health is well documented. Over 22,000 references relating only to L-ascorbic acid have appeared since 1966. 

This synthesis was the first step toward industrial vitamin production, which began in 1936. The synthetic product was shown to have the same biological activity as the natural substance. It is reversibly oxidized in the body to dehydro-L-ascorbic acid (3) (L-// fi (9-2,3-hexodiulosonic acid y-lactone), a potent antiscorbutic agent with hiU vitamin activity. In 1937, Haworth and Szent-Gyn rgyi received the Nobel Prize for their work on vitamin C. 

Chemical Properties. The most significant chemical property of L-ascorbic acid is its reversible oxidation to dehydro-L-ascorbic acid. Dehydro-L-ascorbic acid has been prepared by uv irradiation and by oxidation with air and charcoal, halogens, ferric chloride, hydrogen peroxide, 2,6-dichlorophenolindophenol, neutral potassium permanganate, selenium oxide, and many other compounds. Dehydro-L-ascorbic acid has been reduced to L-ascorbic acid by hydrogen iodide, hydrogen sulfide, 1,4-dithiothreitol (l,4-dimercapto-2,3-butanediol), and the like (33). 

In acidic solution, the degradation results in the formation of furfural, furfuryl alcohol, 2-furoic acid, 3-hydroxyfurfural, furoin, 2-methyl-3,8-dihydroxychroman, ethylglyoxal, and several condensation products (36). Many metals, especially copper, cataly2e the oxidation of L-ascorbic acid. Oxalic acid and copper form a chelate complex which prevents the ascorbic acid-copper-complex formation and therefore oxalic acid inhibits effectively the oxidation of L-ascorbic acid. L-Ascorbic acid can also be stabilized with metaphosphoric acid, amino acids, 8-hydroxyquinoline, glycols, sugars, and trichloracetic acid (38). Another catalytic reaction which accounts for loss of L-ascorbic acid occurs with enzymes, eg, L-ascorbic acid oxidase, a copper protein-containing enzyme. 

Most current industrial vitamin C production is based on the efficient second synthesis developed by Reichstein and Grbssner in 1934 (15). Various attempts to develop a superior, more economical L-ascorbic acid process have been reported since 1934. These approaches, which have met with htde success, ate summarized in Crawford s comprehensive review (46). Currently, all chemical syntheses of vitamin C involve modifications of the Reichstein and Grbssner approach (Fig. 5). In the first step, D-glucose (4) is catalytically (Ni-catalyst) hydrogenated to D-sorbitol (20). Oxidation to L-sotbose (21) occurs microhiologicaRy with The isolated L-sotbose is reacted with acetone and sulfuric acid to yield 2,3 4,6 diacetone-L-sorbose,... 

L-Sorhose to 2-KGA Fermentation. In China, a variant of the Reichstein-Grbssner synthesis has been developed on an industrial scale (see Fig. 5). L-Sorbose is oxidized direcdy to 2-ketogulonic acid (2-KGA) (24) in a mixed culture fermentation step (48). Acid-catalyzed lactonization and enolization of 2-KGA produces L-ascorbic acid (1). 

Because of the time and expense involved, biological assays are used primarily for research purposes. The first chemical method for assaying L-ascorbic acid was the titration with 2,6-dichlorophenolindophenol solution (76). This method is not appHcable in the presence of a variety of interfering substances, eg, reduced metal ions, sulfites, tannins, or colored dyes. This 2,6-dichlorophenolindophenol method and other chemical and physiochemical methods are based on the reducing character of L-ascorbic acid (77). Colorimetric reactions with metal ions as weU as other redox systems, eg, potassium hexacyanoferrate(III), methylene blue, chloramine, etc, have been used for the assay, but they are unspecific because of interferences from a large number of reducing substances contained in foods and natural products (78). These methods have been used extensively in fish research (79). A specific photometric method for the assay of vitamin C in biological samples is based on the oxidation of ascorbic acid to dehydroascorbic acid with 2,4-dinitrophenylhydrazine (80). In the microfluorometric method, ascorbic acid is oxidized to dehydroascorbic acid in the presence of charcoal. The oxidized form is reacted with o-phenylenediamine to produce a fluorescent compound that is detected with an excitation maximum of ca 350 nm and an emission maximum of ca 430 nm (81). 

Ascorbic acid is involved in carnitine biosynthesis. Carnitine (y-amino-P-hydroxybutyric acid, trimethylbetaine) (30) is a component of heart muscle, skeletal tissue, Uver and other tissues. It is involved in the transport of fatty acids into mitochondria, where they are oxidized to provide energy for the ceU and animal. It is synthesized in animals from lysine and methionine by two hydroxylases, both containing ferrous iron and L-ascorbic acid. Ascorbic acid donates electrons to the enzymes involved in the metabohsm of L-tyrosine, cholesterol, and histamine (128). 

Ascorbic acid is a reasonably strong reducing agent. The biochemical and physiological functions of ascorbic acid most likely derive from its reducing properties—it functions as an electron carrier. Loss of one electron due to interactions with oxygen or metal ions leads to semidehydro-L-ascorbate, a reactive free radical (Figure 18.30) that can be reduced back to L-ascorbic acid by various enzymes in animals and plants. A characteristic reaction of ascorbic acid is its oxidation to dehydro-L-aseorbie add. Ascorbic acid and dehydroascor-bic acid form an effective redox system. 

Vitamin C or L-ascorbic acid (Fig. 1) is chemically defined as 2-oxo-L-theo-hexono-4-lactone-2,3-enediol. Ascorbic acid can be reversibly be oxidized to semidehydro- L-ascorbic acid and further to dehydroas-corbic acid. 

A. Pentoses.—t-Ascorbic acid 2- and 3-phosphates, together with their phosphate esters, give a characteristic colour with ferric chloride and this colour reaction has been used in a study of the hydrolysis of L-ascorbic acid 3-phosphate (58). The acid-catalysed, pseudo-firsi-order hydrolysis proceeds with P—O bond fission, as does the bromine oxidation of its phenyl ester. Both of these observations can be rationalized if (58) is... 

The problem of selectivity is the most serious drawback to in vivo electrochemical analysis. Many compounds of neurochemical interest oxidize at very similar potentials. While this problem can be overcome somewhat by use of differential waveforms (see Sect. 3.2), many important compounds cannot be resolvai voltammetrically. It is generally not possible to distinguish between dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) or l tween 5-hydroxytryptamine (5-HT) and 5-hydroxyindolacetic acid (5-HIAA). Of even more serious concern, ascorbic acid oxidizes at the same potential as dopamine and uric acid oxidizes at the same potential as 5-HT, both of these interferences are present in millimolar concentrations... 

The methylated analog CXV of L-ascorbic acid, 2,5-dimethyl-A4-D-glucosaccharo-3,6-lactone methyl ester has been obtained by simultaneous enolization and methylation of a number of substances. For instance it is derivable by treatment, with silver oxide and methyl iodide, of D-glucosaccharo-1,5 3,6-dilactone (CIX), D-glucosaccharo-1,4 ... 

By analogy with the biosynthesis of L-ascorbic acid and with other oxidation-reduction enzyme systems, it seems likely that D-galactose is oxidized to D-galacturonic acid (XXIII) on reduction at Cl, this yields L-galactonic acid (XXIV), the 1,5-lactone (XXV) of which, on reduction at Cl, would give L-galactose (XXII). 

Amao MB, Cano A, Hemandez-Ruiz J, Garcia-Canovas F and Acosta M. 1996. Inhibition by L-ascorbic acid and other antioxidants of the 2,2 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) oxidation catalyzed by peroxidase a new approach for determining total antioxidant status of foods. Anal Biochem 236(2) 255—261. 

Bakke and Theander132 described an interesting, new synthesis of L-ascorbic acid by one-step oxidation of 1,2-O-isopropylidene-a-D-glucofuranose to l,2-0-isopropylidene-a-D-xyfo-5-hexulofuranurono-6,3-lactone hydrate (74), followed by hydrolysis of the isopropyli-dene group, and specific, borohydride reduction of the aldehyde group liberated. 

A number of electron-transfer reactions of biological interest have been studied using high-pressure techniques (4, 5). These include the oxidation of L-ascorbic acid by [Fe(CN)6]3- (148), [Fe(CN)5N02]3 - (149), and Fe(phen)2(CN)2] (150). The first two reactions are characterized by volumes of activation of -16 and 10 cm3 mol-1, respectively, which indicate that solvent rearrangement as a result of an increase in electrostriction must account for the volume collapse on going to... 

D-glucose and of the fact that 9 and 25 differ only in the oxidation state at C-l and C-6 [the relationship between 9 and 25 was originally recognized by Fischer and Piloty8, and it subsequently played a major role1 in the development of practical syntheses of L-ascorbic acid (6) from D-glucose (25) by carbon-chain inversion that is, reduction at C- ... 

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. 

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