Of nicotinic acid

Commercially, pyridine is manufactured from ethyne and ammonia. It is used as a solvent, particularly in the plastics industry, in the manufacture of nicotinic acid, various drugs and rubber chemicals. 

P-Picoline may serve as an important source of nicotinic acid [59-67-6] for dietary supplements. A variety of substituted pyridines may be prepared from acrolein (75—83). 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

The alkyl pyridines (6) and (7) can be transformed either to nicotinic acid or nicotinonitrile. In the case of nicotinic acid, these transformations can occur by either chemical or biological means. From an industrial standpoint, the majority of nicotinic acid is produced by the nitric acid oxidation of 2-meth5i-5-ethylpyridine. Although not of industrial significance, the air oxidation has also been reported. Isocinchomeronic acid (10) (Fig. 2) is formed as an intermediate. 

Nicotinic acid has also been produced by microbial means from the nitrile. Phodococcus (44,45) has frequendy been used in this regard. Interestingly, irradiation of a CoTynebacterium suspension during the fermentation led to higher yields of nicotinic acid (46). 

Both nicotinic acid and nicotinamide have been assayed by chemical and biological methods. Owing to the fact that niacin is found in many different forms in nature, it is important to indicate the specific analyte in question. For example, if biological assay procedures are used, it is necessary to indicate whether the analysis is to determine the quantity of nicotinic acid or if niacin activity is the desired result of the analysis. If nicotinic acid is desired, then a method specific for nicotinic acid should be used. If quantitation of niacin activity is the desired outcome, then all compounds (bound and unbound) which behave like niacin will assay biologically for this substance (1). 

The Kixnig reaction (Fig. 5) has been used to determine the amount of nicotinic acid and niacinamide. In this procedure, quatemization of the pyridine nucleus by cyanogen bromide is followed by ring opening to generate the putative dialdehyde intermediate. Reaction of this compound with an appropriate base, such as p-rr ethyl am in oph en o1 sulfate (47) or sulfanilic acid (48), generates a dye. The concentration of this dye is deterrnined c olo rime trie ally. 

For more specific analysis, chromatographic methods have been developed. Using reverse-phase columns and uv detection, hplc methods have been appHed to the analysis of nicotinic acid and nicotinamide in biological fluids such as blood and urine and in foods such as coffee and meat. Derivatization techniques have also been employed to improve sensitivity (55). For example, the reaction of nicotinic amide with DCCI (AT-dicyclohexyl-0-methoxycoumarin-4-yl)methyl isourea to yield the fluorescent coumarin ester has been reported (56). After separation on a reversed-phase column, detection limits of 10 pmol for nicotinic acid have been reported (57). 

Owing to poor volatihty, derivatization of nicotinic acid and nicotinamide are important techniques in the gc analysis of these substances. For example, a gc procedure has been reported for nicotinamide using a flame ionisation detector at detection limits of - 0.2 fig (58). The nonvolatile amide was converted to the nitrile by reaction with heptafluorobutryic anhydride (56). For a related molecule, quinolinic acid, fmol detection limits were claimed for a gc procedure using either packed or capillary columns after derivatization to its hexafluoroisopropyl ester (58). 

From a bioavailabihty standpoint, the fact that a significant amount of nicotinic acid is in a bound form has important biological consequences. Poor bioavailabihty stems from the fact that the ester linkage is resistance to digestive enzymes. In the case of com, this condition can be alleviated if com is pretreated with alkah. This food preparation method is frequently practiced in Mexico for the preparation of tortillas. 

Despite stmctural similarities, the pharmacological consequences of excesses of these substances are quite different. Due to the interest in the effects of nicotinic acid on atherosclerosis, and in particular its use based on its abiUty to lower semm cholesterol, the toxicity of large doses of nicotinic acid has been evaluated. Eor example, in a study designed to assess its abiUty to lower semm cholesterol, only 28% of the patients remained in the study after receiving a large initial dose of 4 g of nicotinic acid due to intolerance at these large doses (70). 

Nicotinyl alcohol (3-pyridinylcarbinol, 3-pyridinemethanol) (27) has use as an antilipemic and peripheral vasodilator. It is available from either the reductions of nicotinic acid esters or preferably, the reduction of the nitrile to the amine followed by dia2otation and nucleophilic displacement. It is frequently adininistered in the form of the tartrate (Eig. 7). Nicotinic acid is frequently used as a salt in conjunction with basic dmgs such as the peripheral vasodilator xanthinol niacinate (28). Nicotinic acid and its derivatives have widespread use as antihyperlipidemic agents and peripheral vasodilators (1). 

Bakers inactive dry yeast is also widely used in the food industry. This yeast may be grown specifically as a food supplement and consequently there is a choice in its composition by varying growth conditions and feedstock makeup. It can possibly produce high levels of nicotinic acid and thiamin, the cmde protein content can be raised to 50—55% and it can be used as a vehicle for the incorporation of micronutrients such as selenium or chromium into the diet. 

When trigonelline is heated in closed tubes with baryta water at 120°, it gives rise to methylamine, whilst similar treatment with hydrochloric acid at 260° furnishes methyl chloride and nicotinic acid (pyridine-3-carboxylic acid), indicating that it is the methylbetaine of nicotinic acid. 

Tobacco and its alkaloids have long ceased to have any therapeutic importance, but their extensive use as insecticides and the demand for nicotine for the manufacture of nicotinic acid have stimulated interest in processes of extraction and methods of estimation. On the latter subject there is a voluminous literature, of which critical resumes have been published by various authors.Recent work on this subject has been specially concerned with (1) the development of miero- and semi-miero-methods suitable for estimating nieotine in tobacco smoke and the distribution of nieotine on sprayed garden produce, in treated soils and in tobaeeo leaves,(2) the study of conditions necessary to ensure satisfactory results in using particular processes, " and (3) methods of separation and estimation of nicotine, nomicotine and anabasine in mixtures of these bases. ) In the United States and in Russia considerable interest is being shown in the cultivation of types of tobacco rich in nicotine, in finding new industrial uses for tobacco and its alkaloids, and in possible by-products from tobacco plants such as citric and malic acids, i " Surveys of information on tobacco alkaloids have been published by Jackson, i Marion and Spath and Kuffner. ... 

Some approaches to the directed search of drugs on the basis of nicotinic acid 99KFZ(4)6. 

Methylation of nicotine to the pyridinium iodide with methyl iodide, followed by its conversion to the hydroxide with silver oxide in water, oxidation with potassium permanganate to the A -methyl nicotinic acid hydroxide and subsequent deprotonation with silver oxide yielded Trigollenine as colorless needles (1897CB2117). In a later publication, the formation of nicotinic acid from nicotine was described. Esterification followed by aminolysis and methylation yielded the A -methylnicotinamide... 

Replacement of one of the benzene rings by pyridine in the fenamic acid-type analgesics leads to an agent with full pharmacologic activity. Treatment of the N-oxide of nicotinic acid with phosphorus trichloride followed by hydrolysis of the acid... 

Aluminum nicotinate is prepared by dissolving nicotinic acid in hot water and adding a slurry of aluminum hydroxide to it. A slight excess of aluminum hydroxide is used in order that the final product would be free of nicotinic acid. The precipitate is collected on a filter and dried. The final product contains a mixture of aluminum nicotinate and a small but acceptable amount of aluminum hydroxide. 

To a solution of 93.8 g of the monoglycol ester in 500 ml of benzene, there are added 55 g of nicotinic acid chloride and 25 g of trimethylemine dissolved in 200 ml of benzene. The solution is stirred gently at a temperature of 60°C for two hours. After this time, the solution is cooled and washed successively with water, dilute hydrochloric acid, dilute ammonia and water until neutrality, it is dried over anhydrous sodium sulfate, and the sol vent Is evaporated under vacuum In this wey llOg of glycol 2-(p-chlorophenoxy)-2-methylpropionate nico-tlnate Is prepared, which represents a yield of 84%. The product is a sllghly yellow oil having a refraction index of no = 1.5422 and which is distilled with decomposition et 214°C at a pressure of 0.3 mm. 

To a mixture of 60 cc of benzene, 40 cc of pyridine and 17 g of hydrochloric acid salt of nicotinic acid chloride, was added 4.5 g of 2,2,6,6-tetramethylolcyclohexanol, and the whole mixture was refuxed at 75°C to 80°C for 2.5 hours. After the mixture was cooled water was added. Precipitate formed was separated by filtration, washed thoroughly with water and dried. Recrystallization from dilute acetic acid gave 14gof the final compound, melting point 177°Cto 180°C. 

For purpose of purification, the hot alcoholic solution is mixed with 975 parts by weight of nicotinic acid while being stirred and heated until the nicotinic acid is completely dissolved. 

Nicotinic acid, HC6H402N (JCa = 1.4 X 1CT5) is another name for niacin, an important member of the vitamin B group. Determine [H+] in a solution prepared by dissolving 3.0 g of nicotinic acid (MM = 123.11 g/mol), HNic, in enough water to form 245 mL of solution. 

Niacin. Figure 1 Structure of nicotinic acid and nicotinamide. 

Dilworth GL (1982) Properties of the selenium-containing moiety of nicotinic acid hydroxylase from Clostridium barkeri. Arch Biochem Biophys 219 30-38. 

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