Tyrosine, alkaloid precursor

The precursors of true alkaloids and protoalkaloids are aminoacids (both their precursors and postcursors), while transamination reactions precede pseudoalkaloids (Tables 1 and 10). It is not difficult to see that from all aminoacids only a small part is known as alkaloid precursors (Table 19). Both true and proto alkaloids are synthesized mainly from the aromatic amino acids, phenylalanine, tyrosine (isoquinoline alkaloids) and tryptophan (indole alkaloids). Lysine is the... 

In plants, cinnamic and p-coumaric acids and their derivatives are ubiquitous. These compounds, in turn, give rise to phenylpropanoids, lignans, lignin, flavonoids, and tannins. Both phenylalanine and tyrosine are precursors to numerous alkaloids. 

Certain alkaloid precursors such as indole derivatives, purines, and nicotinic acid are powerful growth stimulators, and some, such as certain phenylalanine-tyrosine derivatives, are inhibitors. The biosynthetic con-... 

The benzylisoquinoline skeleton is formed from two molecules of tyrosine, and one of these molecules is utilized via dopamine (Fig. 4). From the work of Professor Zenk and his colleagues it is now clear that the other tyrosine molecule is used either via 4-hydroxyphenylacetaldehyde (20) or 3,4-dihydroxyphenylacetaldehyde (21) yielding, respectively, (22) or norlaudanosoline (23) (Schumacher et al. 1983). It is worth noting that labelled norlaudanosoline (23) was the first compound ever to be tested as an alkaloid precursor apart from a-amino acids and closely related compounds (Battersby et al. 1964). The successful study of plant alkaloid biosynthesis with advanced precursors was built upon that first successful experiment, which was... 

Degradation of 5 and 57 revealed that both skeletons are built from two C6-C2 units derivable from tyrosine (81,82). Many 14C-labeled isoquinolines, which on biogenetic grounds could be possible late precursors of both alkaloids, were prepared and fed to Stephania japonica plants, after which the labeled alkaloids were isolated. Isoquinolines 59-64, lacking the... 

Tyrosine is also the metabolic precursor to the neurotransmitter dopamine and the catecholamine hormones norepinephrine (noradrenaline) and epinephrine (adrenaline), as well as to the alkaloids in opium, including morphine. 

True alkaloids derive from amino acid and they share a heterocyclic ring with nitrogen. These alkaloids are highly reactive substances with biological activity even in low doses. All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid. True alkaloids form water-soluble salts. Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as N-oxides. These alkaloids occur in a limited number of species and families, and are those compounds in which decarboxylated amino acids are condensed with a non-nitrogenous structural moiety. The primary precursors of true alkaloids are such amino acids as L-ornithine, L-lysine, L-phenylalanine/L-tyrosine, L-tryptophan and L-histidine . Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine, dopamine, morphine and usambarensine (Figure 4). A fuller list of examples appears in Table 1. 

Figure 12. L-tyrosine, with its aromatic side chain, is a precursor of phenylethylamino- and isoquinoUne alkaloids.

Tyrosine is an important precursor of alkaloids with the phenyl and phenylpropyl nuclei. There are four basic alkaloid pathways. 

Arguing from structural similarities, it was originally suggested (10) that the Cephalotaxus alkaloids could be derived in vivo from the same precursor as the aromatic erythrina bases, but since Cephalotaxus and homoerythrina alkaloids have been isolated (90) from E. wilsoniana, it has been postulated (10b, 89) that both groups have a 1-phenethyltetrahydroisoquinoline as a common precursor (Scheme 36). Tyrosine is incorporated (122) into cepha-lotaxine, but the labeling pattern did not seem to be consistent with a... 

Dopamine may alternatively be formed from tyrosine via hydroxylation of L-dopa which is decarboxylated. However, inverse isotope dilution experiments to study the formation of dopamine and dopa have shown that this is probably a minor pathway in peyote (176). It has been shown that L-tyrosine is incorporated into alkaloids in peyote three times more efficiently than into protein (344). 4-Hydroxy-3-methoxyphenethylamine can be methylated to 3,4-dimethoxy-phenethylamine (homoveratrylamine), which may be viewed as a dead-end product in Scheme 2 (10, 203). Phenylalanine is probably not a precursor of the... 

The most abundant alkaloid in Coryphantha macromeris, normacromerine, has been shown to originate from tyrosine (330). Tyramine and JV-methyltyramine are efficiently incorporated into normacromerine while octopamine and dopamine are poor precursors. Norepinephrine, epinephrine, normetanephrine, and meta-nephrine have all been shown to be biosynthetically incorporated into normacromerine, and they have also been shown to be naturally occurring trace intermediates in this cactus species (331, 334). Normacromerine is only slowly converted to macromerine in C. macromeris (332). The results indicate that alternative pathways to normacromerine exist precise conclusions regarding the biosynthesis of normacromerine must await further studies. 

The Rutaceae oxazoles are evidently derived from /V-nicotinoyl-p-(p-hydroxy)-phenylethylamide (51), with the exception of balsoxin (25) and texamine (26) in which the nicotinoyl moiety is replaced by benzoyl. The condensation of these tyramine and nicotinic acid residues does not represent any major departure from the standard routes of alkaloid biosynthesis in the Rutaceae, for it has long been recognized that the alkaloids of this family are all derived from either phenylalanine (52), tyrosine, (53), or anthranilic acid (54) (22), the latter being the acknowledged precursor to nicotinic acid in most organisms (23). The formation of the putative oxazole precursor 51 or its equivalent therefore constitutes a convergence of the two predominant modes of alkaloid biosynthesis in the family. 

Cephalotaxus Alkaloids.—Preliminary results indicate that the homo-Erythrina alkaloid schelhammeridine (52) derives from phenylalanine and tyrosine by way of a phenethylisoquinoline precursor [as (53)].52 Previous evidence for the biosynthesis of the related alkaloid cephalotaxine (54), obtained with tyrosine labelled in the side-chain, has indicated a different pathway which involves two molecules of this amino-acid.53 Recently, however, tyrosine labelled in the aromatic ring was examined as a cephalotaxine precursor and was found54 to label ring A of (54) almost exclusively, i.e. only one unit of tyrosine is used for biosynthesis. This is obviously inconsistent with the previous evidence and the early incorporations are... 

Further detail on the biosynthesis of corynoline (78) and related alkaloids is that (76) is a precursor for corynoline (78) and corycavine (77).64 In the latter case it was observed that the configurations at C-13 and C-14 in the precursor were unimportant and incorporation occurred via the metho-salt. Tetrahydro-corysamine (76) is closely related to corydaline, whose biosynthesis from tyrosine and methionine has been studied.66 The C-methyl group at C-13 was shown to arise from methionine and the mechanism suggested for the methylation involves... 

Phenanthroindolizidine Alkaloids.—The phenanthroindolizidine alkaloids, e.g. tylophorine (14) and tylophorinine (15), are assembled in Tylophora asthmatica from fragments derived from ornithine, phenylalanine, and tyrosine (cf. Vol. 8, p. 6 Vol. 9, p. 5). The last amino-acid is the source of ring B plus C-9 and C-10. It has now been shown that dopa is a better precursor than tyrosine for this fragment. Label from [2-14C]dopa was specifically incorporated into C-10 of (14) and (15).16... 

Alkaloids thus represent one of the largest groups of natural products, with over 10,000 known compounds at present, and they display an enormous variety of structures, which is due to the fact that several different precursors find their way into alkaloid skeletons, such as ornithine, lysine, phenylalanine, tyrosine, and tryptophan (38-40). In addition, part of the alkaloid molecule can be derived from other pathways, such as the terpenoid pathway, or from carbohydrates (38-40). Whereas the structure elucidation of alkaloids and the exploration of alkaloid biosynthetic pathways have always commanded much attention, there are relatively few experimental data on the ecological function of alkaloids. This is the more surprising since alkaloids are known for their toxic and pharmacological properties and many are potent pharmaceuticals. 

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