Pantothenic acid salts

Although deficiency conditions are known, and although addition of pantothenic acid salts to food is known to improve the nitrogen balance, few efforts have been made so far to supplement foods with this vitamin. Recent smdies indicate that the increased use of processed foods has reduced the pantothenic acid levels in the diet of industrial countries, which suggests the future need for pantothenic acid supplements (25). 

R)-Pantothenic acid (1) contains two subunits, (R)-pantoic acid and P-alanine. The chemical abstract name is A/-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)-P-alanine (11). Only (R)-pantothenic acid is biologically active. Pantothenic acid is unstable under alkaline or acidic conditions, but is stable under neutral conditions. Pantothenic acid is extremely hygroscopic, and there are stabiUty problems associated with the sodium salt of pantothenic acid. The major commercial source of this vitamin is thus the stable calcium salt (3) (calcium pantothenate). 

The bulk of the industrial supply of the calcium salt of (R)-pantothenic acid is used in food and feed enrichment. Food enrichment includes breakfast cereals, beverages, dietetic, and baby foods. Animal feed is fortified with calcium-(R)-pantothenate which functions as a growth factor. 

The major producers of the calcium salt of pantothenic acid and panthenol are Hoffmann-La Roche, Daiichi, BASF, and Alps. Racemic panthenol is used mainly in hair care products, whereas (R)-panthenol is exclusively used in top-of-the-line, more expensive skin and hair care products. The current (ca 1997) price of (R,3)-panthenol varies between 12 and 18 per kg, that of D-panthenol varies between 30 and 45 per kg, and that of D-calcium pantothenate (Calpan) varies between 22 and 30 per kg. 

R-(+)-Pantothenic acid sodium salt (7V-[2,4-dihydroxy-3,3-dimethylbutyryl] P-alanine Na salt) [867-81-2] M 241.2, [aJ +27.1 (c 2, H2O), pK 4.4 (for free acid). Crystd from EtOH, very hygroscopic (kept in sealed ampoules). The free acid is a viscous hygroscopic oil with [a] +37.5 (c 5, H2O), easily destroyed by acids and bases. 

Numerous new salts and additive compounds of cinchona alkaloids, and especially of quinine, have been described, of which only a few can be mentioned as examples quinine additive compounds with sulph-anilamide, t quinine salts of (+) and (—)-pantothenic acid, °( > quinine sulphamate and disulphamate, °( organo-mercury compounds of quinine and cinchonine such as quinine-monomercuric chloride. Various salts and combinations of quinine have also been protected by patent, e.g., ascorbates and nicotinates. 

CN (/ )-iV-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)- 3-alanine calcium salt (2 1) Pantothenic acid... 

Pantothenic acid (Figure 19.19) is known also as vitamin Bj. It is A-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)- 3-alanine. It occurs in nature only in the o-form. Free pantothenic acid and its sodium salt are chemically unstable, and therefore the usual pharmacological preparation is the calcium salt (calcium pantothenate). The latter is stable in neutral solutions but it is destroyed by heat and acid solution. 

More recently [635], a unique extraction step in supplemented foods, by using hot water and a precipitation solution, following by HPLC-ELD/UV analysis has been performed for the simultaneous determination of pyridoxine, thiamine, riboflavin, niacin, pantothenic acid, folic acid, cyanoco-balamin, and ascorbic acid. The mobile phase consisting of phosphate buffer and methanol has been modified in order to perform ion-liquid chromatography by adding l-octanesulfonic acid sodium salt. Furthermore, triethylamine has been also added to improve peak symmetry. 

D-(+)-Pantothenic acid calcium salt (A-[2,4-dihydroxy-3,3-dimethylbutyryl] P-alanine... 

D-(+)-Pantothenic acid calcium salt (A-[2,4-dihydroxy-3,3-dimethylbutyryI] p-alanine calcium salt) [137-08-6] M 476.5, m 195-196°, 200-201°, [a]20 +28.2° (c 5, H20). It forms needles on recrystn from MeOH, EtOH or isoPrOH (with 0.5mol of isoPrOH). Moderately hygroscopic. The... 

Pantothenic acid 10-15 mg/day. Deficiency causes apathy, depression, impaired adrenal function, and muscular weakness, co -Methylpantothenic acid is a specific antagonist. The calcium salt, calcium pantothenate, is the usual commercial form. 

Two aliphatic acids possess, for grasses, many of the growth-distortion and toxicity effects associated with the synthetic auxins on dicotyledonous plants. Trichloroacetic acid and 2,2-dichloropropionic acid (dalapon), as the sodium salts, have been called grass "hormones or auxins, although Wilkinson184 could find no growth stimulation at low concentrations, and described dalapon as an antiauxin from its interference with indole-3-acetic acid effects. The herbicidal properties of trichloroacetate do not depend on its protein-denaturing ability, and those of 2,2-dichloropropionic acid involve, at least indirectly, the synthesis of pantothenic acid. 

Pantothenic acid is produced commerdally by synthesis involving the condensation of d-pantolactone with salt of -alanine. Some of the dietary supplement forms include caldum pantothenate, dexpanthenol, and panthenol. 

The process of racemization has a number of practical application in the laboratory and in industry. Thus, in the synthesis of an optical isomer it is frequently possible to racemize the unwanted isomer and to separate additional quantities of the desired isomer. By repeating this process a number of times it is theoretically possible to approach a 100% yield of Synthetic product consisting of only one optical isomer, An example of the utilization of such a process is found in the production of pantothenic acid and its salts, In this process the mixture of D- and L-2-hydroxy-3,3-butyrolactones are separated. The D-lactone is condensed with the salt of beta-alanine to give the biologically active salt of pantothenic acid, The remaining L-lactone is racemized and recycled. 

D-Pantolactone (Figure 6.3.1) is an important intermediate in the production of d-pantothenic acid, also called vitamin B5. Deficiency of pantothenic acid can result in symptoms such as pathological changes of the skin and mucosa, disorders in the gastrointestinal tract and nervous system, organ changes, and hormonal disorders. Pantothenic acid is used mainly in feed for chicken and pigs and also as a vitamin supply in human nutrition. Its commercial form, the calcium salt, is produced worldwide on a multi-thousand ton scale. 

D-Pantothenic acid is also traditionally produced by chemical processes which involve efficient but troublesome and costly crystallization of diastereomeric salts of pantoate and chiral amines. After lactonization of the isolated D-pantoate, d-pantolactone is reacted with / -alanine to give D-pantothenate. Because the monovalent salts of pantothenic acid are highly hygroscopic, conversion into the calcium salt is essential for convenient formulation. The third class of synthetic processes for optically active compounds makes use of biotechnology. For natural com-... 

Nicotinamide D-Pantothenic acid (hemiCa salt) 6.10 11.90 Vitamin B12 0.0135... 

Calcium Pantothenate occurs as a slightly hygroscopic, white powder. It is the calcium salt of the dextrorotatory isomer of pantothenic acid. It is stable in air. One gram dissolves in about 3 mL of water. It is soluble in glycerin, but is practically insoluble in alcohol, in chloroform, and in ether. 

R)-Pantothenic acid (vitamin B5) is synthesized by microbes and plants, but not by mammals, who require it as a nutritional factor. Only the (R)-enantiomer is physiologically active. (R)-Pantothenic acid is produced as its calcium salt on a 6 kt a-1 scale, 80% of which is applied as an animal feed additive major suppliers are Roche, Fuji and BASF. Pantothenic acid is produced via chemical methods [110] but a fermentative procedure has recently been commercialized. 

Free pantothenic acid and its sodium salt are chemically unstable, and therefore the usual pharmacological preparation is the calcium salt (calcium... 

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