Ascorbic acid ester derivatives

Modern antioxidant technology is merely about 70 years old. Only four synthetic antioxidants are widely used in foods, namely the phenolic antioxidants BHA, BHT and diphenol TBHQ (which are antioxidants of low polarity), while more polar antioxidants are esters of gallic acid (gallates) and esters of ascorbic acid. Polar antioxidants are ascorbic and erythorbic acids and their salts. Ascorbic acid, its derivatives and its analogue erythorbic (isoascorbic) acid are described in Section 5.13.1. 

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 ... 

While esters of sulfuric acid do not play as central a role in metabolism as do phosphate esters, they occur widely. Both oxygen esters (R-0-S03 , often referred to as O-sulfates) and derivatives of sulfamic acid (R-NH-SOg, N-suIfates) are found, the latter occurring in mucopolysaccharides such as heparin. Sulfate esters of mucopolysaccharides and of steroids are ubiquitous and sulfation is the most abundant known modification of tyrosine side chains. Choline sulfate and ascorbic acid 2-sulfate are also found in cells. Sulfate esters of phenols and many other organic sulfates are present in urine. 

One of the main problems of topical application of vitamin C is that it is extremly unstable, so hydrophilic derivatives like sodium ascorbyl phosphate and lipophilic esters with fatty acids were synthesized to improve stability.43,44 However, an efficient increase in vitamin C levels after topical application of different ascorbic acid derivatives including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid to porcine skin could not be shown.42... 

These are just a few of the many chemical reactions of the hexoses. Gluconic acid, glucono-5-lactone from this acid, sorbitol, sorbitol esters, sorbitans (tetra-hydric anhydrosorbitol), mannitol, mannitol esters, copolymers of fatty acid sorbitol esters and alkylene oxides, and a few other derivatives are currently marketed as commodity chemicals derived from the hexoses. Vitamin C (l-ascorbic acid) is perhaps one of the best examples of a commercial derivative of D-glucose that is manufactured primarily by chemical synthesis ... 

Synthesis of Ascorbic acid and of Disaccharides (i) The synthesis of Vitamin C (75), ascorbic acid from D-galactose (ref.72) and that from D-glucose (ref.73) were described in the same year which also saw the development of the the latter as an industrial route. Sorbitol obtained by the reduction of D-glucose was oxidised with the bacterium Acetobacter suboxvdans to L-sorbose which as the bis-acetonylidene derivative was next oxidised to the corresponding acid, L-2-oxogulonic acid, the methyl ester of which was base-catalysed to afford the final product as illustrated. 

Among the salts in the ascorbate series is also Ba 2-O-sulfonato-L-ascorbate dihydrate that is derived from the ascorbic acid 2-sulfate ester. This biologically important compound (17) was much debated because it was diflScult to decide whether the sulfate group was attached to C2 or C3. The structural analysis by McClelland (18) proved the site to be at C2 as shown in Figure 7. The bond lengths, angles, and resonance forms are clearly similar to those of the simple ascorbate anions irrespective of the effect of the sulfate group attached to C2. 

A survey of work since 1975 on the derivatization of ascorbic acid is reviewed from the perspective of the organic chemistry of ascorbic acid. Recent advances in the control of regioselectivity of alkylative derivatization of ascorbic acid have been made possible by the utilization of di- and trianions of ascorbic acid. Their use has allowed the facile synthesis of inorganic esters of ascorbic acid. New synthesis of acetal and ketal, side-chain oxidized, and deoxy derivatives are reviewed. The total synthesis of a new side-chain oxidized ascorbic acid derivative, 5-ketoascorbic acid, is reported. 

Researchers have used C NMR spectroscopy to assign structure to several ester and ether derivatives of I. That method is particularly useful to diflFerentiate 2-0- and 3-0-substituted derivatives of I because ionization of the OH3 induces the large downfield shift of C3, as previously discussed. Thus, 2-0-methyl-L-ascorbic acid, but not 3-0-methyl-L-ascorbic acid, showed a 16-ppm change in the chemical shift of C3 when the pH values of their solutions were changed from 2 to 7 (Table II). At pH 7, the chemical shifts of the C3 carbons in L-ascorbate (II) and in its 2-sulfate and 2-phosphate esters were similar in magnitude (Table II). 

We have used the growth effects and pathologies associated with L-ascorbic acid deficiency as a basis for the determination of the biological potency of related compounds (Table I). At a dietary concentration of 0.5 mM, L-ascorbic acid and dehydroascorbic acid were fully active, as well as some ester derivatives including the 6-myristate and 2-phosphate compounds. The insect may be metabolically like the guinea pig because both were able to utilize those esters (17), Carboxylesterases and phosphatases probably converted those derivatives to the free vitamin (18). The 6-bromo compound was less active and apparently cannot be metabolized to L-ascorbic acid or only poorly so. 

Several ascorbic acid derivatives were examined by Pensabene et al. (570) for their ability to inhibit nitrosation of pyrrolidine in a model system developed to simulate the lipid-aqueous-protein composition of bacon. While sodium ascorbate was quite effective in the aqueous phase, a combination of an ascorbyl ester with sodium ascorbate gave a better effect in the lipid phase (Table XX). The use of ascorbates and tocopherol as inhibitors of nitrosamine formation and oxidation in foods of the aqueous and lipid type has been reviewed by Newmark and Mergens (326). These compounds in combination could be markedly useful in preventing food contamination with nitrosamines and/or nitros-amides in cured meats such as bacon. 

More traditional O2 oxidation experiments were attempted with the vaulted iron and manganese complexes in several solvents with many of the reducing agents (ascorbic acid, sodium ascorbate, thiols, borohydride, and amalgamated zinc) that have been used elsewhere in work with porphyrins and their derivatives. " The more promising systems are mentioned here. Various thiols, such as thioglycol ethyl ester and P-mercaptoethanol, were... 

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