Amines important

Among the more important amine derivatives found in the body are a group of compounds known... 

Catalytic hydtogenation is the most efficient method for the large scale manufacture of many aromatic and ahphatic amines. Some of the commercially important amines produced by catalytic hydrogenation include aniline (from nitrobenzene), 1,6-hexanediamine (from adiponitrile), isophoronediamine (from 3-nitro-l,5,5-trimethylcyclohexanecarbonitrile), phenylenediamine (from dinitrobenzene), toluenediamine (from dinitrotoluene), toluidine (from nitrotoluene), and xyhdine (from nitroxylene). As these examples suggest, aromatic amines ate usually made by hydrogenating the... 

The commercial interest in epoxide (epoxy) resins was first made apparent by the publication of German Patent 676117 by I G Farben in 1939 which described liquid polyepoxides. In 1943 P. Castan filed US Patent 2 324483, covering the curing of the resins with dibasic acids. This important process was subsequently exploited by the Ciba Company. A later patent of Castan covered the hardening of epoxide resins with alkaline catalysts used in the range 0.1-5% This patent, however, became of somewhat restricted value as the important amine hardeners are usually used in quantities higher than 5%. 

Kindler, K. Peschke, K. (1934) New and Improved Methods for the Synthesis of Pharmacologically Important Amines. IX. Synthesis of Papaverine and Tetrahydropapaverine. Archiv fur... 

Hepatic steatosis usually is a result of excessive administration of carbohydrates and/or lipids, but deficiencies of carnitine, choline, and essential fatty acids also may contribute. Hepatic steatosis can be minimized or reversed by avoiding overfeeding, especially from dextrose and lipids.35,38 Carnitine is an important amine that transports long-chain triglycerides into the mitochondria for oxidation, but carnitine deficiency in adults is extremely rare and is mostly a problem in premature infants and patients receiving chronic dialysis. Choline is an essential amine required for synthesis of cell membrane components such as phospholipids. Although a true choline deficiency is rare, preliminary studies of choline supplementation to adult patients PN caused reversal of steatosis. 

Incomplete conversion was observed at lower temperatures and significant amounts of undesired decomposition products were obtained at temperatures in excess of 150 °C. These processes were applied to the synthesis of biologically important amine-containing compounds such as the seratonin 5-HT4 agonist SC-53116. 

In addition to alkenes and alkynes, allenes have attracted considerable interest due to their unique reactivity and multireaction sites. Therefore, transition-metal-catalyzed nucleophilic addition reaction of amines and imines to allenes has been extensively studied to prepare biologically important amines and nitrogen-heterocycles.31,31d... 

For a more detailed overview of electrochemical detection, the interested reader is referred to Kissinger [59]. The range of applications snitable for electrochemical detection are discnssed in an excellent review by Pacakova and Stulik [60]. Perhaps the most biomedically important application is the determination of catecholamines in bioflnids [61-63]. Electrochemical detection has also lent itself to the detection of other medically important amines snch as histamine [64] and nenrotrans-mitters [65]. Additionally, electrochemical detection has been applied to the detection of certain antibiotics [66] and environmental carcinogens [67]. 

To make use of the Mannich reaction it is possible to methylate the N-atom of the new side chain and eliminate trimethylamine. The product, a 3-methyleneindoleninium salt, can then be trapped with suitable nucleophiles. In the example shown in Scheme 7.7b, cyanide ion is used, and reduction of the resultant nitrile yields the important amine trypta-mine. Indol-3-ylacetonitrile is also the source of indol-3-ylacetic acid and other biologically useful compounds (see Section 7.1.7). 

A second mechanism in the. aging of CTPB propellants also exists and proceeds concurrently with the reactions proposed above. It consists of an attack at the reactive points of unsaturation in the backbone polymer, which causes additional crosslinking and hence an increase in propellant modulus, particularly at the surface. The exposed surface of CTPB propellants changes, as indicated by an increase in hardness. Heavy metal ions are particularly harmful, and it was found that an increase from 10 to 80 p.p.m. of iron caused a significant increase in surface hardening by catalytic attack on the double bonds. Antioxidants in general provide sufficient protection for polymer storage. In CTPB propellants the antioxidant selected to protect the double bond is very important. Amine-type antioxidants have provided better surface stability than phenolic compounds. 

This increase in water solubility on conversion of an amine to its protonated salt has enormous practical consequences in drug delivery. Many important amine-containing drugs, such as morphine (a painkiller) and tetracycline (an antibiotic), are insoluble in aqueous body fluids and are thus difficult to deliver to the appropriate site within the body. Converting these drugs to their ammonium salts, however, increases their solubility to the point where delivery through the bloodstream becomes possible. 

The two general reactions can be used to prepare a variety of compounds in which two aryl groups are linked. The unsymmetrical biaryls are of particular interest since they are not as accessible through other reactions as the symmetrical compounds. Some conception of the types of compounds available by replacement of the amino group of aromatic amines by aryl groups can be obtained from an examination of the following table, which shows the more important amines from which diazo... 

The chemical structures of important amines for curing epoxy resins in adhesive systems are identified in Fig. 5.1. Diethylenetriamine (DETA), triethylenetetramine (TETA), ra-aminoethylpiperazine (AEP), diethylaminopropylamine (DEAPA), ra-phenylenediamine (MPDA), and diaminodiphenyl sulfone (DDS) are the most commonly used members of this class. They are all primary amines. They give room or elevated temperature cure at near stoichiometric ratios. Ethylenediamine is too reactive to be used in most practical adhesive formulations. Polyoxypropyleneamines (amine-terminated polypropylene glycols) impart superior flexibility and adhesion. 

Many drugs and other biologically important amines are commonly stored and used as their salts. Amine salts are less prone to decomposition by oxidation and other reactions, and they have virtually no fishy odor. The salts are soluble in water, and they are easily converted to solutions for syrups and injectables. 

The major enzyme involved in the formation of ammonia in the liver, brain, muscle, and kidney is glutamate dehydrogenase, which catalyzes the reaction in which ammonia is condensed with 2-oxoglutarate to form glutamate (Sec. 15.1). Small amounts of ammonia are produced from important amine metabolites such as epinephrine, norepinephrine, and histamine via amine oxidase reactions. It is also produced in the degradation of purines and pyrimidines (Sec. 15.6) and in the small intestine from the hydrolysis of glutamine. The concentration of ammonia is regulated within narrow limits the upper limit of normal in the blood in humans is 70/tmol L-1. It is toxic to most cells at quite low concentrations hence there are specific chemical mechanisms for its removal. The reasons for ammonia toxicity are still not understood. The activity of the urea cycle in the liver maintains the concentration of ammonia in peripheral blood at 20/ molL. ... 

Amino acid decarboxylations are involved in the synthesis of several metabolically important amines, e.g., 5-hydroxytryptamine (serotonin) from tryptophan, histamine from histidine, and y-aminohutyric acid (GABA) from glutamate. 

An important amination reaction involves hydroxy-substituted naphthalenes (Fig. 13.53). In a process known as the Bucherer reaction, naphthols are heated under pressure with a mixture of ammonia and sodium bisulfite. As... 

Among the most important amine functional epoxy curing agents are the polyami-doamine resins. These are made from dimerized unsaturated fatty acids by reaction of the dimer acid with a polyamine such as diethylenetriamine. 

In addition to the cholinergic and glutaminergic reticular neurons already described as ebbing and flowing in concert with the rest of the centrencephalic core, the brain stem also contains the important aminer-gic nuclei, the locus coeruleus (secreting norepinephrine) and the raphe... 

Many important amines have been obtained by the hydrolysis of one of these substances. Thus, r-butylamine is formed by alkaline hydrolysis of f-butylurea (78%) or by treatment of r-butylisothiocyanate with formic acid (79%). Allylamine is synthesized by hydroiysis of ailyl isocyanate with dilute hydrochloric acid (73%). The hydroiysis of isocyanates, urethanes, and ureas, which occur as intermediates in the degradation of amides and azides, has been discussed under methods 446 and 447, where many examples have been cited. 

Acetylation of antibiotics is a common mechanism of modification. The acyltransferases generally use the metabolically abundant acetyl-CoA as the preferred acyl-donor. The aminoglycoside antibiotic acetyltransferases (AACs), for example, modify important amines that make contact with the target 16 S rRNA (Fig. 9), which results in a loss of positive charge and increased steric bulk that contribute to lowering the affinity of the antibiotics for the rRNA target by 600-fold (26). The AACs are members of the GCN5 superfamily of acyltransferases that include such members as the eukaryotic histone acetyltransferases and serotonin acetyltransferase (27). 

Monoamine oxidase, which exists in two distinct forms, referred to as MAO A and MAO B, is one of the enzymes responsible for the degradation of biologically important amines. Compounds that block the catalytic action of MAO A, which is selective for the degradation of norepinephrine and serotinin, have antidepressant effects whereas compounds that inhibit MAO B, which degrades dopamine in the brain, are useful for treating Parkinson s disease [190, 191]. Both MAO A and MAO B contain flavin co-enzyme attached at the 8-a-position to an enzyme-active cysteine residue (54). A one-electron transfer mechanism (Scheme 15) for the oxidations catalyzed by MAO was first proposed by Silverman [192] and Krantz [193,194]. 

Some of the simplest and most important amines are prepared on an industrial scale by processes that are not practicable as laboratory methods. 

Ion-exchange chromatography is a separation method based on the exchanging of ions in a solution with ions of the same charge present in a porous insoluble solid. The method is used for the deionization of water [1,2], It is often employed for the separation and identihcation of the rare earth and transuranium elements [2], Additionally, ion-exchange chromatography is also used in clinical laboratories for the automated separation and analysis of amino acids and other physiologically important amines used for pharmaceutical purposes [3],... 

In a gas chromatographic study on biologically important amines, Fales and Pisano1 investigated some indole bases, such as tryptamine and serotonine. When the indole bases were gas chromatographed on a 0.75 % SE-30 column on Gas Chrom P, extensive tailing was observed, probably due to adsorptive interactions between the compound and the support. However, when a thicker layer of SE-30 was used (4 %) the compounds showed well-formed peaks without tailing. 

Histamine is probably the most important amine with physiological effects for human health. Ingested daily in small amounts, it normally degrades, but it still can induce a drastic response in a number of sensitive people inducing symptoms, such as skin redness, headache, nausea, stomach disorder, and respiratory troubles, this is a pathology known as Histamine Intolerance. Usually people affected by this disorder... 

The synthesis of fluorinated analogs of biologically important amines has been explored extensively. Their direct preparation is difficult since most of the common fluorination agents can also react with the amino group. However, by the use of appropriate solvents, like liquid hydrogen fluoride which protects the amine functionality by protonation, successful... 

The local anesthetic novocaine, which is often used in dentistry and for minor surgery, is injected as an amine salt. See A Clinical Perspective Medically Important Amines. 

---