Hordenine biosynthesis

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. 

Fig. 1. Distribution of radioactivity among phenolic amines during 3 months after feeding [l-14C]tyramine to a Cleopatra mandarin seedling. ( — ) Hordenine, (0—0) synephrine, (O—O) AJ-methyltyramine, and (O—O) tyramine. (Reprinted with permission from Phytochemistry, Vol. 8, T. A. Wheaton and 1. Stewart, Biosynthesis of synephrine in citrus. Copyright 1969, Per-gamon Journals Ltd.)...

Several substances have been detected in the course of Amarylli-daceae alkaloid isolations which cannot be classified within any of the previous sections. Of these, belladine and 0-methylnorbelladine are basic substances of singular importance in the biosynthesis of the alkaloids of the family. Further discussion of these bases is reserved for Section X. Hordenine has been isolated from Pancratium maritimum (3) and Ungernia victoris (61). It appears to be a metabolite of tyrosine, an important amino acid percursor of the alkaloids of the family. Ismine, C15H15NO3 (mp 99.5°-100.5° [a]p +0° in CHCI3 picrate, mp 158°-159°), has been isolated from an unidentified Ismene spp., Crinum powellii, and Sprekelia formosissima in minute amounts (6). 

On the other hand, it was clarified by the incorporation of labeled methionine that the methyl groups incorporated during the biosynthesis of N-methyltyramine and hordenine were derived from methionine.The yield of N-methyltyramine in these experiments is less than half that of horde-nine however, the incorporation of into N-methyltyramine is 1.5 times that of hordenine. This indicates that N-methyltyramine is not formed by the demethylation of hordenine, but that N-methyltyramine was formed first, and hordenine is then formed by the methylation of the former alkaloid. If N-methyltyramine was formed by the demethylation of hordenine, the incorporation rate of of N-methyltyramine, which possesses only one N-methyl moiety, and is present in lower yield than hordenine, should not be superior to that of hordenine [4]. 

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. 

Biogenic amines are a group of aliphatic, aromatic or heterocychc bases derived from amino acids, which exhibit a variety of biological effects, as they perform different functions in animal and plant tissues. Some biogenic amines are building materials for the biosynthesis of phytohormones of the auxin group, plant protoalkaloids (such as hordenine and gramine), true alkaloids and other secondary plant metabolites. In animal tissues they have the function of tissue hormones (e.g. histamine) and are precursors of adrenal hormones (catecholamines). 

Erythrina berterona. However, more recently a hydroxylase has been isolated from spinach which catalyses the direct conversion of L-phenylalanine to L-tyrosine . Studies on the biosynthesis of selected alkaloids using isotopically labelled L-phenylalanine as a precursor also indicated that hydroxylation of L-phenylalanine to give L-tyrosine is possible in peyote and barley . In barley, for example, it was established that L-phenylalanine, L-tyrosine and tyramine (45) were precursors of the alkaloid hordenine (47) and the biosynthetic sequence (42 - 44 45 - 46 47) was inferred. 

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