Dehydro-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. 

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). 

L-fhreo-2,3-Hexodiulosono-1,4-lactone (dehydro-L-ascorbic acid) 2-(p-bromophenyl)hydrazone DASCBH 37 386... 

Reaction of dehydro-L-ascorbic acid and its analogs with two molecules of o-phenylenediamine or its substituted derivative gave the quinoxaline... 

Reaction of dehydro-L-ascorbic acid with guanidine derivatives gave the 2-aminoimidazole acyclo-C-nucleoside analog 1213, as shown in Scheme 241 (92T6385). 

The trihydroxypropyl derivative 63 was prepared from dehydro-L-ascorbic acid phenylosazone (62) by opening the lactone ring with warm alkali and acidifying the mixture after a few minutes, whereupon the pyrazolinone 63 separated immediately.63 The structure of this compound was established by degradation,63 and confirmed by a study of its n.m.r. spectrum.64 The p-tolyl-, p-(bromophenyl)-, and p-(iodophenyl)-osazones of dehydro-L-ascorbic acid were also converted into the corresponding l-aryl-4-phenylazo-3-(trihydroxy-propyl)-5-pyrazolinone, and their acetylation and benzoylation products were prepared.64... 

L-Ascorbic Acid (AA) Dehydro-L Ascorbic Acid (DHAA)... 

AA = L-ascorbic Acid DHAA = dehydro-L-ascorbic Acid. 

The product analysis of L-ascorbic acid irradiated in deaerated solution is restricted to the measurement of dehydro-L-ascorbic acid, hydrogen, and the decrease in L-ascorbic acid.263 To account for the fact that N20 has no effect on G(L-ascorbic acid consumption), a rather complex mechanism has been put forward that also allows the formation of a reduction product (L-gulono-1,4-lactone, suggested but not measured). 

Katznelson and coworkers494 noted that 96 is a positional isomer of dehydro-L-ascorbic acid (105), as is evident when 96 is depicted in the 1,4-lactone fonn 106 (which, presumably, could exist as 107 or 108). On the basis of polarographic data, Bernaerts and De Ley522 suggested... 

Treatment of dehydro-L-ascorbic acid (72) with phenyl hydrazine followed by hydroxylamine yielded the hydrazone oxime (73a), cyclization of which in refluxing acetic anhydride gave 4-[l-//u< o-2,3-diacetoxy-(l-hydroxypropyl)]-2-phenyl-l,2,3-triazole-5-carboxylic acid lactone (74a) <77CAR(59)141>. Analogous reactions of the derivatives (72) with substituted aryl hydrazines yielded the triazoles (74b-d). Alternatively, the hydrazone oximes (73a-d) may be treated with HBr in... 

L-ascorbic acid (Figure 9-9) is a lactone (internal ester of a hydroxycarboxylic acid) and is characterized by the enediol group, which makes it a strongly reducing compound. The D form has no biological activity. One of the isomers, D-isoascorbic acid, or erythorbic acid, is produced commercially for use as a food additive. L-ascorbic acid is readily and reversibly oxidized to dehydro-L-ascorbic acid (Figure 9-10), which retains vitamin C activity. This compound can be further oxidized to diketo-L-gulonic acid, in a... 

Crystalline dehydro-L-ascorbic acid (3) is reported to exist as the dimer (11) (26). In water, it is present as the hemiacetal monomer (12). 

Kenyon, J., and Munro, N. (194B). The isolation and some properties of dehydro-L-asCOrbic acid. /. ClrcHr. Sec. Part 1, pp. 158-161. 

N oo o CD p-Bromophenylhydrazine of monomeric dehydro-L-ascorbic acid Ci2Hii05N2Br i25)... 

An improved synthesis of dehydroascorbic acid has been reported (42). The oxidation of ascorbic acid in absolute methanol with oxygen over activated charcoal catalyst is reported to aflFord 28 in 95% yield. Dehydroascorbic acid has been characterized in solution as the monomer, 28 (43), and as the dimer (44,45) and its tetra acetyl derivative 29 (46). Several studies of mono- and di-hydrazone (48-53) and osazone (54) derivatives of dehydroascorbic acid have been reported. Hydrazone derivatives of dehydroascorbic acid have been used in the reductive synthesis of 2,3-diaza-2,3-dideoxy- and 2-aza-2-deoxyascorbic acid derivatives 30, 31, and 32 (55,56). Recently the reaction product of dehydro-L-ascorbic acid and L-phenylalanine in aqueous solution has been isolated and identified as tris(2-deoxy-2-L-ascorbyl)amine, 33, based on spectral and chemical data and its symmetry properties (57). 

Tolbert and Ward have reviewed the NMR data on dehydro-L-ascorbic acid in chapter 5 in this book. 

---