Amino Derivatives of Ascorbic Acid

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. - 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 

High antiscorbutic power is also reported to be shown by a derivative of L-ascorbic acid in which the enolic hydroxyl group at C2 is replaced by an amino group. 3,4-Isopropylidene-L-threonic acid (LX), prepared from 5,6-isopropylidene-L-ascorbic acid, is converted into the 2-acetyl- 

4-isopropylidene-L-threonyl chloride (LXI) and this is then allowed to react with the sodium derivative of ethyl malonate. 

Hydrolysis of the condensate gives LXIII and this by the agency of methyl alcoholic alkali affords the enol form of 2-desoxy-L-ascorbic acid (LXIV). When the latter is allowed to react with benzene diazonium chloride there is formed the mono(phenylhydrazone) LXV from which 

Both the monoamino and the diamino analogs of ascorbic acid exhibit powerful reducing properties, and the monoamino compound has a high antiscorbutic activity, probably due to the fact that it undergoes conversion to L-ascorbic acid in vivo by a process of deamination. 

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A reference to 6-amino-6-deoxy derivatives of ascorbic acid is covered in Chapter 9. 

Bromophenol blue (3.0...4.6) aliphatic carboxylic acids [225 — 228] malonic and lactic acids [229] palmitic and lactic acids [230] malonic, glycolic, malic, citric, tartaric, ketoglutaric, galacturonic and oxalic acids [196] dicarboxylic acids, succinic acid [231] indoleacetic acid, trichloroacetic acid [232] palmitic acid, palmityl- and stearyllactic acid [223] benzoic, sorbic and salicylic acid [234] metabolites of ascorbic acid [235] chloropropionic acid [236] oligogalacturonic acids [237] amino acids, hydrocarbons, mono-, di- and triglycerides [238] xylobiose, xylose, glucose and derivatives [239] sugar alcohols [91] toxaphene [240]... 

Folic acid is itself inactive it is converted into the biologically active coenzyme, tetrahydrofolic acid, which is important in the biosynthesis of amino acids and DNA and therefore in cell division. The formyl derivative of tetrahydrofolic acid is folinic acid and this is used to bypass the block when the body fails to effect the conversion of folic acid (see Folic acid antagonists, p. 606). Ascorbic acid protects the active tetrahydrofolic acid from oxidation the anaemia of scurvy, although usually normoblastic, may be megaloblastic due to deficiency of tetrahydrofolic acid. 

The brown pigments which were formed through the oxidative pathway are almost twice those formed through the anaerobic pathway. This effect could be derived from the involvement of H2O2 and oxy--radicals in the aerobic oxidation pathway of ascorbic acid (20,21). The oxy-radicals may generate carbonyls and amino acid free radicals which, by polymerization, could accelerate the formation of more brown pigments. 

Oxalate is a terminal product of normal metabolism. When [ " C]oxalate is injected, most of the labeled compound is excreted, and only a small fraction of the radioactivity is recovered in bone and muscle. There are only two immediate precursors of oxalic acid in normal metabolic pathways glyoxylic acid and 2,3-diketo-L-gulonic acid. The first of these compounds is the product of amino acid oxidation (serine and glycine), and the second is derived from the oxidation of ascorbic acid (see Fig. 3-25). 

About 300 individual compounds with antimutagenic properties are known. The frequency of mutations can be reduced by some amino acids (arginine, histidine, methionine, cysteamine etc ), vitamins and provitamins (a-tocopherol, ascorbic acid, retinol, p-carotene, phylloquinone, folic acid), enzymes (peroxidase, NADPH oxidase, glutathione peroxidase, catalase), complex compounds of plant and animal origin, chemical substances with antioxidant properties (derivatives of gallic acid, ionol, oxypyridines, selenium salts and others). 

Knowledge of metabolic pathways of phenylalanine and tyrosine has been obtained by study of certain inborn errors of metabolism in man (see Chapter 5). Of particular interest in human nutrition is the relationship of ascorbic acid and folic acid in the metabolism of these two amino acids. In premature infants or in persons with scurvy, the feeding of high protein diets or the administration of tyrosine leads to hydroxyphenyluria. Both ascorbic acid and folic acid (large doses) will prevent the excretion of abnormal quantities of hydroxyphenyl derivatives. Recently, Sealock... 

Ktnetec (48) determined ascorbic acid, DHA, acetylsalicylic acid, and its degradation product, salicylic acid, from pharmaceuticals. He used UV detection for the measurement of ascorbic acid, acetylsalicylic acid, and fluorescence detection with the exitation wavelength set at 350 nm and emission wavelength set at 430 nm for measurement of the quinoxaline derivative of o-phenylenediamine and DHA. The o-phenylenediamine reagent was eluted as an unretained compound in the amino column thus causing no interference with other compounds in either UV or fluorescence detection. The detection limit was about 0.002 mg/ mL of sample, the injection volume was 20 pL. 

Along with stomach, bile, and lactic acids, there are many other acids in the human body These include, but are not limited to, nucleic acids, amino acids, fatty acids, and vitamins such as folic and ascorbic acids. Nucleic acids, including RNA (ribonucleic acid) and DNA (deoxyribonucleic acid), are long chains of phosphates and sugar to which nucleotide bases are attached. The phosphate molecules in the backbone of RNA and DNA are derived from phosphoric acid. Therefore, DNA is very weakly acidic. 

Protons are mainly derived from two sources—free acids in the diet and sulfur-containing amino acids. Acids taken up with food— e.g., citric acid, ascorbic acid, and phosphoric acid—already release protons in the alkaline pH of the intestinal tract. More important for proton balance, however, are the amino acids methionine and cysteine, which arise from protein degradation in the cells. Their S atoms are oxidized in the liver to form sulfuric acid, which supplies protons by dissociation into sulfate. 

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