Phenylethylamine molecule

Photoirradiation of a single crystal of l(S)-2 maintained the initial transparency, confirming the single-crystal-to-single-crystal transformation. Finally, a piece of single crystal (1.28 x 0.21 x 0.09 mm3) of 1 - S)-2 was submitted to X-ray crystallographic analysis at 293 K before and after successive irradiation at >290 nm at 293 K [23]. The absolute structure was determined on the basis of the S configuration of the phenylethylamine molecule 2. The reaction proceeded smoothly and was completed after irradiation for 45 min. The crystal data are summarized in Table 27.1. 

FIGURE 4.24 Adsorption chromatography of small molecules with a TSK-GEL G2500PWxl column. Column TSK-GEL G2500PWxl, 6 /tm, 7.8 mm X 30 cm. Sample (I) phenylacetic acid. (2) 3-phenylpropionic acid, (3) 4-phenylbutyric acid, (4) benzylamine, (5) 2-phenylethylamine, (6) 3-phenylpropylamine, (7) benzyl alcohol, (8) 2-phenylethanol, and (9) 3-phenyl-1 -propanol. Elution 0.1 M NaCIO, in water. Flow rate 2.0 ml/min. Temperature 65 C. Detection UV at 215 nm. 

Molecules having only a sulfoxide function and no other acidic or basic site have been resolved through the intermediacy of metal complex formation. In 1934 Backer and Keuning resolved the cobalt complex of sulfoxide 5 using d-camphorsulfonic acid. More recently Cope and Caress applied the same technique to the resolution of ethyl p-tolyl sulfoxide (6). Sulfoxide 6 and optically active 1-phenylethylamine were used to form diastereomeric complexes i.e., (-1-)- and ( —)-trans-dichloro(ethyl p-tolyl sulfoxide) (1-phenylethylamine) platinum(II). Both enantiomers of 6 were obtained in optically pure form. Diastereomeric platinum complexes formed from racemic methyl phenyl (and three para-substituted phenyl) sulfoxides and d-N, N-dimethyl phenylglycine have been separated chromatographically on an analytical column L A nonaromatic example, cyclohexyl methyl sulfoxide, did not resolve. 

Hormones are generally quite small molecules, and are chemically uncomplicated. Examples include adrenaline (II) and /3 -phenylethylamine (III). 

Experiments by Kenyon and Blois, with samples of phenylalanine labelled with i4C at each of the three aliphatic carbon positions, showed that the molecule could photolyse at each of the three exocyclic carbon-carbon bonds. Decarboxylation was also thought to be an important process, but unfortunately no resulting phenylethylamine was detected during this work. Mechanisms for the production of the observed products were suggested [24],... 

Competitive inhibitors bind to specific groups in the enzyme active site to form an enzyme-inhibitor complex. The inhibitor and substrate compete for the same site, so that the substrate is prevented from binding. This is usually because the substrate and inhibitor share considerable stmctural similarity. Catalysis is diminished because a lower proportion of molecules have a bound substrate. Inhibition can be relieved by increasing the concentration of substrate. Some simple examples are shown below. Thus, sulfanilamide is an inhibitor of the enzyme that incorporates j9-aminobenzoic acid into folic acid, and has antibacterial properties by restricting folic acid biosynthesis in the bacterium (see Box 11.13). Some phenylethylamine derivatives, e.g. phenelzine, provide useful antidepressant drags by inhibiting the enzyme monoamine oxidase. The cA-isomer maleic acid is a powerful inhibitor of the enzyme that utilizes the trans-isomer fumaric acid in the Krebs cycle. 

Other electrochemical processes of organic compounds on Pb electrodes or electrodes with UPD Pb have been studied - formaldehyde [323], oxalic acid [386], trichloro- and trifluoroethane [387], 1-phenylethylamine [388], 3-hydroxychi-nuclidine [388], dichlorodifluoromethane [389], polychlorobenzenes [390], 1-propa-nol [391], pyrrole polymerization [392], and inorganic compounds - phosphine [388] and sulfate(IV) ions [393]. Simultaneous catalytic or inhibiting influence of organic solvents - acetonitrile, dimethyl-sulfoxide, and Pb + presence on electrooxidation of small organic molecules on Pt electrodes has been studied using on-line mass spectroscopy [394],... 

Monoamine oxidase (MAO) (E.C. 1.4.3.4) is an enzyme found in all tissues and almost all cells, bound to the outer mitochondrial membrane. Its active site contains flavine adenine dinucleotide (FAD), which is bound to the cysteine of a -Ser-Gly-Gly-Cys-Tyr sequence. Ser and Tyr in this sequence suggest a nucleophilic environment, and histidine is necessary for the activity of the enzyme. Thiol reagents inhibit MAO. There are at least two classes of MAO binding sites, either on the same molecule or on different isozymes. They are designated as MAO-A, which is specific for 5-HT (serotonin) as a substrate, and MAO-B, which prefers phenylethylamine. Similarly, MAO inhibitors show a preference for one or the other active site, as discussed below. 

Still another experimental route to introducing otherwise excluded molecules into the brain is to chemically modify them so that they are lipophilic and therefore can passively diffuse. The brain, just as most other organs and tissues of the body, has enzymes to metabolize or biotransform metabolites in order to use and then get rid of them. Many of these pathways are oxidative. A reduced species or derivative which is lipophilic can enter the brain by simple passive diffusion there to be oxidatively transformed into an active state. Compounds which have been tested in animals include derivatives of 2-PAM (an antidote for organophosphate insecticide poisoning) and phenylethylamine (similar to amphetamine type molecules). Figure 5 illustrates the general concept behind this method. 

This is a tetrameric copper-containing glycoprotein, which catalyzes the conversion of dopamine into norepinephrine, a hormone/neurotransmitter, and also the hydroxylation of a number of substituted phenylethylamines.1401 1403 Consideration of this enzyme has been hindered by uncertainty over the stoichiometry of binding of copper, and, until recently, there seemed to be good evidence for four copper ions per molecule.1 4 However, there is now convincing support for a stoichiometry of eight copper ions per molecule, with two per subunit.1405,1406 This conclusion is based upon analysis and titration methods. 

Figure 16.2 Dihydropyridine-pyridinium salt redox system for site-specific and sustained delivery to the brain. The prodrug A is delivered directly to the brain, where it is oxidized and trapped as the prodrug B. The quaternary ammonium salt is slowly cleaved by chemical/enzymatic action with sustained release of the biologically active phenylethylamine C and the facile elimination of the carrier molecule D. Elimination of the drug from the general circulation is by comparison accelerated, either as A or B or as cleavage products...

Following on from their previous work on the biomimetic synthesis of marine natural products, Steglich et al. proposed a biomimetic lamellarin synthesis in which an oxidative dimerization of an arylpyruvic acid and condensation of the resulting 1,4-dicarbonyl compound with a suitable 2-arylethylamine would be the key steps of the synthesis. Thus, the synthesis of lamellarin G trimethyl ether was achieved by coupling two molecules of 3-(3,4-dimethoxyphenyl)pyruvic acid and the appropriate 2-phenylethylamine <9579941, 97AG(E)155>. The use of a mixture of two different arylpyruvic acids afforded the unsymmetrical lamellarin L <00MI1147>. 

An efficient method of resolution of diastereomeric mixtures of 5-substituted 2-oxazolidinones, utilizing commercially available (S)-l-phenylethylamine as the optically active portion of the molecule, has been developed16. Thus, the Ar-benzyloxycarbonyl derivative of (S)-TV-(l-phen-ylethyl)-2-propen-1-amine (1), treated with iodine in chloroform, affords the diastereomeric products as a 50 50 mixture which is easily separated by chromatography on silica gel. 

For example, 2-phenylethylamine is a 1 ° amine, so it has only one alkyl group bonded to N. This alkyl group must come from the carbonyl compound, and the rest of the molecule then comes from the nitrogen component. For a 1° amine, the nitrogen component must be NH3. 

Despite this result, proof that tyrosine gave rise to two dissimilar intermediates in the biosynthesis of both berberine and hydrastine was provided by the finding that only one molecule of dopamine is incorporated into these alkaloids (58). Degradation of the labeled berberine, obtained after administering 3,4-dihydroxy-2-phenylethylamine-l- C,... 

Strategy Look at the target molecule, and identify the groups attached to nitrogen. One of the groups must he derived from the aldehyde or ketone component, and the other must be derived from the amine component. In the case of iV-methyl-2-phenylethyl-amine, there are two combinations that can lead to the product idienylacetaldehyde plus methyiamine or formaldehyde plus 2-phenylethylamine. In general, it s usually better to choose the combination with the simpler amine component—methyl-amine in this case—and to use an excess of that amine as reactant. 

The most extensive studies of phenylethylamines have been done by Pullman and coworkers (59,65,67/68). Their PCILO calculations indicated that gauche and trans conformers have nearly identical energies in the majority of phenylethylamines and phenylethanolamines studied. AI studied were carried out using three different basis sets (67) these all indicated a slight but definite preference for gauche conformers. These authors noted the preponderance of extended conformers in crystal structures and in solution they attributed this to environmental forces. To test this hypothesis, computations were repeated with the inclusion of water molecules, and a tendency toward the extended conformation was indeed observed. 

Evaluation of Some Bicyclic Systems as Conformationally-Defined Phenylethylamines. X-Ray Crystallography. Perhaps the ultimate test of the suitability of a chemical structure for preparing conformationally-defined analogs would be their ability to produce biological effects identical to those of the parent compound. Since this ideal is rarely achieved, and since a "wrong" conformer should be inactive, it is useful to have other criteria with which to evaluate these systems. The bicyclic molecules to be examined in the present study are compounds I-VIII (Figure 7), benzobicyclo[2.2.2]octenes, benzobicyclo [2.2.1]heptenes, and 1,2,3,4-tetrahydro-l,4-epoxynaphthalenes. A number of structural parameters... 

The rigidification of the dopamine molecule led to a number of dopamine receptor agonists in which the dopamine molecule, with its phenylethylamine moiety, is readily recognisable. In these dopamine agonists the amine moiety is either a part of a cyclic system, e.g. benzo[/]quinolines, naphthoxazines, and benzopyranoxazines, or an exocyclic amine, e.g. 2-aminotetralins and 2-aminoindans (Chart 1.5). 

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