Phenylethylamines hordenine

The relation of many of the simpler alkaloids to the aromatic amino acids is obvious. For example, germinating barley contains (241), besides tyrosine and tyramine, A -methyltyramine, JViV -dimethyltyramine (hordenine), and the trimethylammonium derivative (candicine). In this simple case the. AT-methylated derivatives are known to be derivable from isotopically labeled tyramine (538) and the methyl groups are known to arise from methionine by transmethylation (540, 586). Similarly AT-methyl derivatives of phenylethylamine, 3,4-dihydroxyphenylethylamine, and 3,4,5-trihy-droxyphenylethylamine are well known alkaloids (cf. review, 701). N-Methylated derivatives of tryptamine and hydroxytryptamine equally occur for example, eserine has an obvious relation to 5-hydroxy tryptamine. Methylated derivatives of metabolites of the aromatic amino acids also occur, for example, trigonelline (67), which is the betaine of nicotinic acid, and damascenine is probably similarly related to hydroxyanthranilic acid. 

As for adrenaline at least, an interruption on the entire respiratory metabolism may be observed, which is reflected on the chemoceptors of the carotid body by the variations of oxygen uptake and carbon dioxide production (148). The direct intervention on the chemoceptors of the carotid and aortic bodies only appears for the nicotinic substances and not for Pervitin (149). The natural sympathomimetics which possess a stimulating influence on the respiration are mainly ephedrine, hordenine, 0-phenylethylamine, and tyramine. 

The difficulties which may be encountered in establishing well-known pathways in a new plant are illustrated by feeding experiments with [2 - " C]tyrosine, [l, 2 - H2]dopamine, and 3-hydroxy-4-methoxy[ar- H]phenylethylamine in E. merkei The conversion of tyrosine into hordenine (63), established in barley could not be demonstrated. Nor were tyrosine and dopamine incorporated into salsoline (55), but all three of the labelled compounds were converted into 3,4-dimethoxyphenylethylamine. These results were rationalized as indicating a pathway that diverged after dopamine with appropriate methylation, giving either salsoline (55) or 3,4-dimethoxyphenylethylamine (a similar branch point is observed in L. williamsii for the biosynthesis of mescaline and tetrahydroiso-quinolines). Further, at the time of the experiments the required methyl-transferases for salsoline and hordenine biosynthesis were apparently blocked. In any event the pathway to 3,4-dimethoxyphenylethylamine is manifestly the dominant one, as this alkaloid and its iV-methyl derivatives are major constituent bases of this plant. 

Hordenine (anhaline, eremursine, peyocactine, 4-[2-(dimethylamino)ethyl]-phenol. For formula, data, and occurrence, see j phenylethylamine alkaloids. H. is biosynthesized from phenylalanine or tyrosine via tyramine and N-methyltyramine. H. is a sympathico-mimetic. It has diuretic effects, at higher doses it increases blood pressure, and is generally similar to ephedrine and tyramine. In addition H. is an antifee-dant for locusts. H. is used as a cardiac stimulant of low toxicity and as a disinfectant in cases of dysentery. Lit. Acta Crystallogr., Sect. C 47,1450 (1991) Beilstein EIV 13. 1790 Hager (5.) 5, 708 f. nj. Nat. Prod. 50, 422 (1987) 53,882 (1990) Karrer, No. 2471 see also phenylethylamine alkaloids. 

Hordenine and iV-methyltyramine are isolates fix)m the young roots of Hordeum vulgare var. hexastichon (Poaceae), and are simple phenylethylamine-type alkaloids. The biosynthetic precursor of these alkaloids is considered to be tyramine, derived from tyrosine. d/-[2- " C]-Tyrosine was fed to H. vulgare var. hexastichon 4 days after germination, and hordenine and N-methyltyramine were isolated after 11 days from the roots. Both alkaloids possessed label at the a-carbon. It was also found that d/-[2- " C]-tyrosine was more effectively incorporated into N-methyltyramine than into hordenine, and no tyramine was detected in the extract. So, the incorporated tyrosine was converted into tyramine and methylated immediately to give N-methyltyramine. Subsequent steps form hordenine by the methylation of N-methyltyramine [3]. 

Both the biosynthesis and chemical synthesis are based on a Mannich condensation of a -phenylethyl-amine derivative with a carbonyl component (Fig.). Depending on the latter, the substituent at Cl can be H-, CH3- or an isoprenoid residue. Several molecules of A. a. can be linked to form oligomers by phenol oxidation, as in pilocereine. As secondary alkaloids, cacti also produce derivatives of p-phenylethylamine, e. g. hordenine and mescaline. 

Hordenine, mhaline A. lV-dimethyltyramine, a widely distributed biogenic amine, m.p. IIT-IIS C, b.p. 173-174 °C. As a derivative of phenylethylamine, H. increases blood pressure, but it has a low physiological activity. 

This important class of pharmacological and clinical agents embraces a rather heterogeneous group of compounds ranging from aliphatic alcohols and aldehydes, xanthines, methylene blue, to a-methylated derivatives of / -phenylethylamine (amphetamine, ephedrine), a-alkylated indolealkylamines and their N-methylated derivatives (hordenine), harmala alkaloids and numerous synthetic drugs derived from hydrazines (Fig. 5). 

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