Amines from amino acids

Chiral lithium amide bases have been used successfully in the asymmetric deprotonation of prochiral ketones [55, 56]. WUliard prepared polymer-supported chiral amines from amino acid derivatives and Merrifield resin [57]. The treatment of cis-2,6-dimethylcyclohexanone with the polymer-supported chiral lithium amide base, followed by the reaction with TMSCl, gave the chiral silyl enol ether. By using polymeric base 96, asymmetric deprotonation occurred smoothly in tetrahydrofuran to give the chiral sUyl enol ether (, S )-102 in 94% with 82% ee (Scheme 3.28). 

Alkynylation. This base (monohydrate) is an excellent catalyst for alkynylation of carbonyl compounds and selective A-monoalkylation of primary amines.- Cesium hydroxide suppresses overalkylation, and therefore is very useful in the exclusive formation of secondary amines from amino acids. 

The dibenzosuberylamine is prepared in quantitative yield from an amine or amino acid and suberyl chloride this chloride has also been used to protect hydroxyl, thiol, and carboxyl groups. Although the dibenzosuberylamine is stable to 5 A HCl/dioxane (22°, 16 h) and to refluxing HBr (1 h), it is completely cleaved by some acids (HCOOH, CH2CI2, 22°, 2 h CE3COOH, CH2CI2, 22°,... 

Difficulties are often encountered in the formation of peptides from a-amino acids which lack an a-hydrogen atom, e.g. a-methylalanine, presumably because of steric hindrance. This problem is obviated by use of the oxazolone 35, an excellent reagent for the addition of a single a-methylalanyl residue to an amine or amino acid [Eq. (22)]... 

Thus, in contrast to benzothiepins, dibenzo compounds can be synthesized by direct acid-catalyzed elimination of water from hydroxy derivatives, or of amines from amino derivatives, at elevated temperatures due to their thermal stability. As in the case of benzothiepins, dibenzo derivatives can also be prepared by base-catalyzed elimination from the corresponding halo derivatives however, the yields are somewhat lower compared to the acid-catalyzed reactions. As a special case, an aziridine derivative was deaminated by palladium-catalyzed hydrogenation to afford the corresponding dibenzothiepin.69... 

It is also possible to prepare them from amino acids by the self-condensation reaction (3.12). The PAs (AABB) can be prepared from diamines and diacids by hydrolytic polymerization [see (3.12)]. The polyamides can also be prepared from other starting materials, such as esters, acid chlorides, isocyanates, silylated amines, and nitrils. The reactive acid chlorides are employed in the synthesis of wholly aromatic polyamides, such as poly(p-phenyleneterephthalamide) in (3.4). The molecular weight distribution (Mw/Mn) of these polymers follows the classical theory of molecular weight distribution and is nearly always in the region of 2. In some cases, such as PA-6,6, chain branching can take place and then the Mw/Mn ratio is higher. 

The polyamines putrescine, cadaverine, spermidine, and spermine, which are seen at elevated levels in some victims of cancer, were separated on a Technicon (The Technicon Company Chauncey, NY) TSM Amino Acid Analyzer packed with an 8% divinylbenzene-co-polystyrene sulfonated resin with post-column ninhydrin detection.111 Amines such as ethanolamine, noradrenaline, hexamethylene diamine, methoxytryptamine, spermine, and spermidine were separated from amino acids on a DC-4A cation exchange resin.112 A similar approach, using a Beckman Model 121M amino acid analyzer equipped with an AA-20 column, was also successful.113 A Polyamin-pak strong cation exchange column (JASCO) was eluted with a citrate buffer for the detection of putrescene, spermine, cadaverine, and 1,5-diaminohex-ane from rat thymus.114 A post-column o-phthaldehyde detection system was used. 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

For example22, separation of enantiomers of chiral molecules (amines, alcohols, amino acids) is possible by using a chiral stationary phase obtained from 10-undecenyl esters of Af-(2-naphthyl)-a-amino acids (4). Amino groups are of fundamental importance in this practical application of the chiral recognition. 

The formation of tluorinated Q -hydroxy-jS-imino esters (180) by treatment of fluorinated imino ethers (179) with lithium 2,2,6,6-tetramethylpiperidide has been reported. A possible explanation for this interesting intramolecular rearrangement is proposed in Scheme 64. Acyclic imides derived from primary benzylic amines and amino acid esters have been found to undergo a novel nitrogen to carbon acyl migration via a base-generated carbanion to yield the corresponding a-amino... 

Biogenic amines arise from amino acids by decarboxylation (see p. 62). This group includes 4-aminobutyrate (y-aminobutyric acid, GABA), which is formed from glutamate and is the most important inhibitory transmitter in the CNS. The catecholamines norepinephrine and epinephrine (see B), serotonin, which is derived from tryptophan, and histamine also belong to the biogenic amine group. All of them additionally act as hormones or mediators (see p. 380). 

Histamine, serotonin, melatonin, and the catecholamines dopa, dopamine, norepinephrine, and epinephrine are known as "biogenic amines."They are produced from amino acids by decarboxylation and usually act not only as hormones, but also as neurotransmitters. 

Klan and coworkers also measured the quantum yield for the photorelease of acids, alcohols, amines, and amino acids from 44, finding that they were released in moderate to low quantum yields in protic and aprotic solvents such as methanol,... 

Efforts have been made to find stereoselective routes which provide disubstituted azetidines. Palladium catalysed cyclization of an enantiomer of allene-substituted amines and amino acids gives the azetidine ester 2 and a tetrahydropyridine in variable yield and ratio, depending on the substituents and conditions <990L717>. The (TRIS)- and (253I )-isomeis of the substituted azetidine-2-carboxylic acids 3 (R = COjH) are obtained in several steps from the corresponding 3 (R = CHjOSiMejBu ) which, in turn, is produced in high yield by photochemical intramolecular cyclization <98HCA1803>. 

A series of chiral amines derived from amino acids has been used the best optical yields have been obtained with phenylalanine derivatives (128) (R1 = CH2C6H5) and tert-leucine tert-butyl ester (129) 146>. 

Amines are nitrogen-containing compounds found in all meteorites that contain amino acids. Their abundances are comparable to those of amino acids, and abundances decrease with increasing numbers of carbon atoms. Similarities between amines and amino acids in the same meteorite have led to the suggestion that amines formed from the amino acids by decarboxylation (loss of the carboxylic acid functional group). This process commonly occurs on heating. 

Many important neurotransmitters are primary or secondary amines, derived from amino acids in simple pathways. In addition, some polyamines that form complexes with DNA are derived from the amino acid ornithine, a component of the urea cycle. A common denominator of many of these pathways is amino acid decarboxylation, another PLP-requiring reaction (see Fig. 18-6). 

There are several classes of alkaloids. Among these are purines such as xanthine and caffeine, ter-penes (Chapter 22), polyketides (Chapter 21), and alkaloids derived from amino acids. The basic amino acids ornithine, arginine, histidine, and lysine as well as the aromatic amino acids, anthranilate, and nicoti-nate are some of the starting materials.199 201 Robinson202 203 in 1917 recognized that many alkaloids are derived directly from aromatic amino acids. He proposed that alkaloids arise from Mannich reactions (Eq. 25-12) in which an amine and an aldehyde (probably through a Schiff base) react with a nucleophilic carbon such as that of an enolate anion. Many of the... 

Importantly, TV-carbamoyl derivatives of primary amines obtained from photolabile benzoins exist in varying proportions as cyclic hydroxyoxazolidinone tautomers. Therefore, the preparation of TV-carbamoyl derivatives of benzoins is applicable only for secondary amines and TV-alkylated amino acids. 244 At basic pH unsymmetrical benzoins, such as 3,5-dimethoxybenzoin, their mixed carbonate and carbamate derivatives, tend to equilibrate to the isomeric forms. Nevertheless, in TFA and aqueous solutions at pH 8 the structural integrity is fully maintained. 244 Preparation of 3,5-dimethoxybenzoin-derived carbamates of secondary amines and amino acids can be mediated by either CDI/methyl triflate in ni-tromethane 246 or 4-nitrophenyl chloroformate/DMAP in dry THF. 244 ... 

Tertiary amines do not react with nitrous acid, acetyl chloride, benzoyl chloride, benzenesulfonyl chloride, but react with alkyl halides to form quaternary ammonium halides, which are converted by silver hydroxide to quaternary ammonium hydroxides. Quaternary ammonium hydroxides upon heating yield (1) tertiary amine pins alcohol (or, for higher members, olefin plus water). Tertiary amines may also be formed (2) by alkylation of secondary amines, e.g., by dimethyl sulfate, (3) from amino acids by living organisms, e g, decomposition of fish in the case of trimethylamine. 

Having accomplished the homogenization of the sample, extraction of free amino acids is usually a simple process of stirring the sample in an appropriate solvent. This is typically a dilute solution (0. IN) of hydrochloric acid (2,7). Elevated temperatures may be used to assist dissolution, but care must be taken not to damage the more acid-labile amino acids. More recently, Moret and Conte (8) report that 0.1N HC1 was not a suitable solvent for all types of food samples. For some types of meat samples, 5% trichloroacetic acid is reported to afford superior performance (for biogenic amines, also amino acids ). It is not unusual to see perchloric acid employed for extraction from meat tissues (also more commonly for biogenic amines). 

The reaction of amines and amino acids with orthophthaldehyde has been widely used in postcolumn and precolumn derivatization in analyses of foods (99-104) and in analyses of peptides from biological samples. Figure 2 (87) presents a chromatogram for OPA derivatives of tryptic peptides from two proteins. The sensitivity of the method was on the order of picomoles. The authors have themselves performed postcolumn OPA derivatization of low-molecular-weight peptides from blue cheeses separated by reversed-phase chromatography (86). 

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