L-ascorbate vitamin

D. S. Soriano, S. David, C. A. Meserole, and F. M. Mulcahy, Catalytic hydrogenation of L-ascorbic (vitamin C) a stereoselective process for the production of L-gulono-1,4-lactone,... 

L-Ascorbic acid sodium salt L-Ascorbic acid, monosodium salt Ascorbicin Ascorbin CCRIS 3291 Cebitate Cenolate Cevalin EINECS 205-126-1 HBL 508 HSDB 694 Iskia-C monosodium ascorbate Monosodium L-ascorbate Natrascorb Natri-C Natrii ascorbas 3-Oxo-L-gulofuranolactone sodium Soda-scorbate Sodium ascorbate Sodium L-ascorbate Vitamin C, sodium salt Vitamin C sodium. Antioxidant in food products. Source of vitamin C. White solid mp = 218° (dec) [a - <-104 soluble in H2O (62 g/100 ml). BASF Corp. EM Ind. Inc. Hoffmann-LaRoche Inc. f er Inc. Spice King Takeda Chem. Ind. Ltd. 

Synonyms L-Ascorbic acid monosodium salt L(+)-Ascorbic acid sodium salt Monosodium ascorbate Monosodium L-ascorbate Sodium L-ascorbate Vitamin C sodium salt... 

Ascorbic Acid [50-81-1] (1) is the name recognized by the lUPAC-IUB Commission on Biochemical Nomenclature for Vitamin C (1). Other names are L-ascorbic acid, L-xyloascorbic acid, and L-// fi (9-hex-2-enoic acid y-lactone. The name... 

L-Ascorbic acid biosynthesis in plants and animals as well as the chemical synthesis starts from D-glucose. The vitamin and its main derivatives, sodium ascorbate, calcium ascorbate, and ascorbyl palmitate, are officially recognized by regulatory agencies and included in compendia such as the United S fates Pharmacopeia/National Formula (USP/NF) and the Food Chemicals Codex (FCC). 

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. 

As a result of having two chiral centers, four stereoisomers of ascorbic acid are possible (Table 1) (Fig. 2). Besides L-ascorbic acid (Activity = 1), only D-araboascorbic acid (erythorbic acid (9)) shows vitamin C activity (Activity = 0.025-0.05). The L-ascorbic acid stmcture (1) in solution and the soHd state are almost identical. Ascorbic acid crystallizes in the space group P2 with four molecules in the unit cell. The crystal data are summarized in Table 2. 

Physical Properties. Table 3 contains a summary of the physical properties of L-ascorbic acid. Properties relating to the stmcture of vitamin C have been reviewed and summarized (32). Stabilization of the molecule is a consequence of delocalization of the TT-electrons over the conjugated enediol system. The highly acidic nature of the H-atom on C-3 has been confirmed by neutron diffraction studies (23). 

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,... 

Reichsteia and Grbssner s second L-ascorbic acid synthesis became the basis for the iadustrial vitamin C production. Many chemical and technical modifications have improved the efficiency of each step, enabling this multistep synthesis to remain the principal, most economical process up to the present (ca 1997) (46). L-Ascorbic acid is produced ia large, iategrated, automated faciUties, involving both continuous and batch operations. The process steps are outlined ia Figure 7. Procedures require ca 1.7-kg L-sorbose/kg of L-ascorbic acid with ca 66% overall yield ia 1977 (55). Siace 1977, further continuous improvement of each vitamin C production step has taken place. Today s overall ascorbic acid yield from L-sorbose is ca 75%. In the mid-1930s, the overall yield from L-sorbose was ca 30%. 

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). 

L-Ascorbic acid is used as a micronutrient additive in pharmaceutical, food, feed, and beverage products, as weU as in cosmetic appHcations. The over-the-counter (OTC) vitamin market is strong, growing in demand, and vitamin C is available in the form of piUs and tablets to supplement the daily diet to maintain peak physical performance. 

In apphcations where vitamin C activity is unimportant, often D-erythorbic acid (D-araboascorbic acid) can also be used, providing the same antioxidant and reducing properties as L-ascorbic acid. 

L-Ascorbic acid, better known as vitamin C, has the simplest chemical structure of all the vitamins (Figure 18.30). It is widely distributed in the animal and plant kingdoms, and only a few vertebrates—humans and other primates, guinea pigs, fruit-eating bats, certain birds, and some fish (rainbow trout, carp, and Coho salmon, for example)—are unable to synthesize it. In all these organisms, the inability to synthesize ascorbic acid stems from a lack of a liver enzyme, L-gulono-y-lactone oxidase. 

The isolation of ascorbic acid was first reported by Albert Szent-Gyorgyi (who called it hexuronie add) in 1928. The structure was determined by ITirst and Haworth in 1933, and, simultaneously, Reichstein reported its synthesis. Haworth and Szent-Gyorgyi, who together suggested that the name be changed to L-ascorbic acid to describe its antiscorbutic (antiscnrvy) activity, were awarded the Nobel Prize in 1937 for their studies of vitamin C. 

Organic acids usually contain a carboxylic acid group, -CO2H. L-Ascorbic acid, commonly known as Vitamin C, is an obvious exception. 

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. 

Vitamin C occurs as L-ascorbic acid and dihydroascorbic acid in fruits, vegetables and potatoes, as well as in processed foods to which it has been added as an antioxidant. The only wholly undisputed function of vitamin C is the prevention of scurvy. Although this is the physiological rationale for the currently recommended intake levels, there is growing evidence that vitamin C may provide additional protective effects against other diseases including cancer, and the recommended dietary allowance (RDA) may be increased in the near future. Scurvy develops in adults whose habitual intake of vitamin C falls below 1 mg/d, and under experimental conditions 10 mg/d is sufficient to prevent or alleviate symptoms (Bartley et al., 1953). The RDA is 60 mg per day in the USA, but plasma levels of ascorbate do not achieve saturation until daily intakes reach around 100 mg (Bates et al., 1979). Most of the ascorbate in human diets is derived from natural sources, and consumers who eat five portions, or about 400-500 g, of fruits and vegetables per day could obtain as much as 200 mg of ascorbate. 

Wang, Y., et al. Human vitamin C (L-ascorbic acid) transporter SVCT1. Biochem. Biophys. Res. Commun. 2000, 267, 488-494. 

Vitamin C or L-ascorbic acid, the antiscorbutic vitamin, has been shown by degradative1 and synthetic methods1 to have the structure I. 

The variation in the antiscorbutic activity displayed by the various analogs of L-ascorbic acid makes it abundantly clear that the activity is dependent upon the stereochemical configuration of the molecule as a whole, and it would appear that the more closely the structure of a particular analog approaches that of the natural Vitamin C the greater will be the antiscorbutic power. Support for this view is illustrated by 6-desoxy-L-ascorbic acid which is obtained from L-sorbose.2 -80 Condensation of L-sorbose with acetone gives a mixture of 2,3-isopropylidene-L-sorbose (LII) and the diisopropylidene derivative. Treatment of LII with p-toluenesulfonyl chloride yields l,6-ditosyl-2,3-isopropylidene-L-sorbose (LIII). The greater reactivity of the tosyl group at C6 enables... 

The conversion of L-xylosone into L-ascorbic acid has been reversed by treating the latter with pert-naphthindan-2,3,4-trione hydrate184 2,3-dioxo-L-zj/fo-hexonic acid is formed and is decarboxylated to L-xylosone. It was suggested that the destruction of ascorbic acid in vivo by this mechanism might explain the relatively high requirements for the vitamin in many species. 

Biosyntheses of hexuronic acids and L-ascorbic acid in plants and animals are closely related. Hexuronic acids, L-ascorbic acid, and L-tartaric acid (a possible precursor of dihydroxyfumaric acid) commonly occur together in plants. If a rat is given chloretone (an antispasmodic), both L-ascorbic acid and D-glucuronic acid are excreted in increased quantity.244 Unlike humans, rats can synthesize their own vitamin C, and are therefore independent of outside sources. Here, D-glucose and D-galactose can be utilized, but not D-mannose. 

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