Nicotinic acid, 6-amino

Not many fine chemicals have a production value exceeding 10 million per year. Less than a do2en achieve production volumes above 10,000 metric tons per year and sales of > 100 million per year. Apart from the pharmaceutical and pesticide fine chemicals these comprise the amino acids (qv), L-lysine and n,T-methionine used as feed additives (see Feeds AND FEED ADDITIVES), and vitamins ascorbic acid and nicotinic acid. 

Craig s synthesis of nicotine (V to VII, p. 42) proceeds via nomicotine. Nicotinic acid nitrile reacts with the Grignard reagent derived from ethyl y-bromopropyl ether to give 3-pyridyl-y-ethoxypropyl ketone (V). This yields an oily oxime (VI) reducible to a-(3-pyridyl)-a-amino-8-ethoxy-w-butane (VII), which with 48 per cent, hydrobromic acid at 130-3° gives womicotine, and this on methylation yields dZ-nicotine. 

A substantial number of bioactive molecules, such as polypeptides, N-acetyl-DL-penicillamine, p-(dipropylsulfamoyl)benzoic acid, and nicotinic acid, contain a carboxylic acid function, and this provides a site for linkage to a polyphosphazene chain. A number of prototype polymers have been synthesized in which pendent amino groups provide coupling sites for the carboxylic acid (34). The amide linkages so formed are potentially bioerodible, but the use of a hydrolytic sensitizing cosubstituent would be expected to accelerate the process. 

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Most cyanogenic glycosides are biogenetically derived from the amino acids phenylalanine, tyrosine, valine, isoleucine, or leucine but the non-protein amino acid cyclopentenylglycine and probably, nicotinic acid also serve as precursors (Figure 5.1) [9]. 

Figure 5.1 Cyanogenic glycosides derived from amino acids (and nicotinic acid)...

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

A. Pastrakuljic, L.O. Derewlany, B. Knie, and G. Koren. The effects of cocaine and nicotine on amino acid transport across the human placental cotyledon perfused in vitro. J Pharmacol Exp Ther. 294 141-146 (2000). 

An intriguing feature of nicotinic acid formation in animals is that it is a metabolite produced from the amino acid tryptophan. This means the pyridine ring is actually formed by biochemical modification of the indole fused-ring system (see Section 11.8.2), and, as you might imagine, it involves a substantial sequence of transformations. 

Pharmaceutically important 3-substituted-[l,8]naphthyridine-2,4-diones have been prepared by the reaction of 2-methyl-477-pyrido[2,3-r/][3,l]oxazin-4-one with active methylene compounds (Scheme 66) <1997J(P1)1487, 2003JOC4567> and by the same group via an intramolecular azadiene-ketene electrocyclization reaction of amino-nicotinic acid derivatives in a related process <2001JOC4413>. 

N.A. Carotene, thiamine, nicotinic acid, riboflavin, folic acid, pantothenic acid, biotin, glutamic acid, serine, glycine, aminobutyric acid, globulin, amino acids.100 An antiseptic, aperient, depurative, digestive, pectoral, a folk remedy for asthma. 

Note No higher nitrated d.erivs of anjinonico-tinic and amino-iso-nicotinic acids were found in Beil... 

T rifluoromethyl-phenyl-amino)-nicotinic acid, 2-[[3-(trifluoromethyl)]amino]-3-pyrodinecarboxylic acid, Ci3H9F3N202, Mr 282.22, mp 204 °C... 

The amino acids believed to be involved in GTF are the constituents of the naturally occurring tripeptide glutathione (256). Anderson et al. have reported a complex of glutathione/nicotinic acid and chromium(III) to be particularly active in their in vitro assay.1198 The complex was described as being purified by HPLC, but the details of the preparation are not available. 

The lack of structural information means that any suggested structure for GTF must be highly speculative. Mertz has suggested1200 that two trans nicotinic acids are coordinated to chromium as illustrated in (258). The first coordination sphere is completed by the various amino adds involved. There is little evidence to support this and it seems unlikely that the hard chromium(III) centre would bind preferentially to the nitrogen group of nicotinic add the idea of N coordination has attracted support and influenced other workers. One product of the reaction of nicotinic acid and chromium(III) (mole ratio 3 1, pH 3.2) has been said to be... 

Niacin is found in unrefined and enriched grains and cereal, milk, aid lean meats, especially liver. Limited quantities of niacin can also be obtained from the metabolism of tryptophan. [Note The pathway is inefficient in that only about 1 mg of nicotinic acid is formed from 60 mg of tryptophan. Further, tryptophan is metabolized to niacin orty when there is a relative abundance of the amino acid—that is, alter the needs for protein synthesis and energy production have been met]... 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

Organic supplements Small amount of vitamins (myo-inositol, thiamine, nicotinic acid, pyridoxine, and so on.), amino acids (usually omitted but sometimes used with advantage), and other undefined supplements (meat, malt, and yeast extract, and protein hydrolysates, and so on.). 

Carbohydrate metabolism provides the main energy source in coccidia. Diets deficient in thiamin, riboflavin, or nicotinic acid—all cofactors in carbohydrate metabolism—result in suppression of parasitic infestation of chickens by E tenella and E acervulina. A thiamin analog, amprolium—1-[(4-amino-2-propyl-5-pyrimidinyl)-methyl]-2-picolinium chloride—has long been used as an effective anticoccidial agent in chickens and cattle with relatively low host toxicity. The antiparasitic activity of amprolium is reversible by thiamin and is recognized to involve inhibition of thiamin transport in the parasite. Unfortunately, amprolium has a rather narrow spectrum of antiparasitic activity it has poor activity against toxoplasmosis, a closely related parasitic infection. 

Pyridopyrimidine systems may also be accessed by in situ generation of pyridylisocyanates <2003TL2745>. Treatment of 2,3-pyridinccarboxylic anhydride with methanol leads to the formation of 2-(methoxycarbonyl)nicotinic acid that undergoes Curtius rearrangement on conversion to the 3-acyl azide with sodium azide and ethyl chloro-formate. Condensation of the resulting isocyanate with a series of amino acids leads to the synthesis of pyrido[3,2- T pyrimidines in good to excellent yield (Scheme 19). 

In humans and animals, chromium(ni) is an essential nutrient that plays a role in glucose, fat, and protein metabolism by potentiating the action of insulin (Anderson 1981). The biologically active form of chromium, called glucose tolerance factor (GTF), is a complex of chromium, nicotinic acid, and possibly amino acids (glycine, cysteine, and glutamic acid). Both humans and animals are capable of converting... 

Facilitated diffusion involves carrier-mediated transport down a concentration gradient. The existence of the carrier molecules means that diffusion down the concentration gradient is much greater than would be expected on the basis of the physicochemical properties of the drag. A much larger number of substances are believed to be transported by facilitated diffusion than active transport, including vitamins such as thiamine, nicotinic acid, riboflavin and vitamin B6, various sugars and amino acids. 

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