Of L-ascorbic acid

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. 

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). 

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. 

Chemical Synthesis. The first synthesis of ascorbic acid was reported ia 1933 by Reichsteia and co-workers (14,39—42) (Fig. 4). Similar, iadependent reports pubHshed by Haworth and co-workers followed shordy after this work (13,43—45). L-Xylose (16) was converted by way of its osazone (17) iato L-xylosone (18), which reacted with hydrogen cyanide forming L-xylonitfile (19). L-Xylonitfile cyclized under mild conditions to the cycloimine of L-ascorbic acid. Hydrolysis of the cycloimine yielded L-ascorbic acid. The yield for the conversion of L-xylosone to L-ascorbic acid was ca 40%. 

L-Xylonitrile Cycloimine of L-ascorbic acid (1) L-Ascorbic acid... 

A Chinese pubHcation (47) with 17 references reviews the use of genetically engineered microorganisms for the production of L-ascorbic acid and its precursor, 2-KGA (49). For example, a 2-keto-L-gulonic acid fermentation process from sorbose has been pubUshed with reported yields over 80% (50). 

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). 

Industrial uses of L-ascorbic acid relate to its antioxidant and reducing properties. It is used as an antioxidant in the commercial preparation of beer, fmit juices, cereals, and caimed and frozen foods, etc. 

Methods for the preparation of L-ascorbic acids having isotopic C, H, O in various positions have been described and reviewed (104,105). Labeled L-ascorbic acid has played an important role in the elucidation of the metaboHc pathway of L-ascorbic acid in plants and animals. 

Fig. 8. Pathway for the biosynthesis of L-ascorbic acid in rats using C-l-labeled D-glucose indicates position of C.

Fig. 10. Suggested pathway for the biosynthesis of L-ascorbic acid (with retention of configuration) in higher plants based on D-glucose-l- C...

Table 4. Content of L-Ascorbic Acid in Representative Foods...

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

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... 

Figure 12.4 Molecular structures of L-ascorbic acid and D-glucose.

Plunkett, A. and Ainsworth, P. (2007). The influence of barrel temperature and screw speed on the retention of L-ascorbic acid in an extruded rice based snack product. /. Food Eng. 78,1127-1133. 

Dailey JW, Gupta PK, Hung CT. 1990. A physiological pharmacokinetic model describing the disposition of lead in the absence and presence of L-ascorbic acid in rats. Toxicol Lett 50 337-348. 

V. Analogs of l-Ascorbic Acid Containing One Enolic Hydroxyl Group. 101... 

The unique feature of L-ascorbic acid and its analogs4 lies in the enediolic system and it is this system which is responsible for the remarkable reducing properties displayed by these substances. 

It will be seen that the enediolic system can theoretically be written in the isomeric 2-keto (II) or 3-keto (III) forms and these in turn are seen to be derived from the 2-keto and the 3-keto acids IV and V, respectively (compare with benzoin which reacts with iodine in an analogous fashion to L-ascorbic acid). Consequently the synthesis of L-ascorbic acid and of its analogs has consisted in devising methods for the formation of 2-keto or 3-keto hydroxy acids followed by their enolization and lactonization. Four main methods are available for the synthesis of analogs of L-ascorbic acid containing the characteristic five-membered unsaturated enediolic ring. 

When the imino compound XIV is heated with dilute hydrochloric acid, hydrolysis of the imino group takes place and there is formed ammonium chloride and D-glucoascorbic acid (XV). The latter displays all the chemical properties of L-ascorbic acid. 

The nomenclature adopted in the designation of the analogs of L-ascorbic acid is based for convenience upon the name of the sugar from which the osone was prepared. For example, D-xylose (XVIII)... 

The process of lactonization and enolization of 2-keto esters under the influence of alkaline reagents has also been applied to the production of analogs of L-ascorbic acid containing a six-membered ring structure.22 For example, methyl 3,4,6-trimethyl-2-keto-D-gluconate (XLI) is treated... 

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