Tyrosine Alkaloids

Isoquinollne alkaloids Tyrosine/DOPA decarboxylase Papaver somniferum... 

Tyrosine- and Phenylalanine-Derived Alkaloids Tyrosine and phenylalanine amino acids are bearing the phenyl-ethylamine moiety of many medicinally relevant alkaloids. Further hydroxylations on the aromatic carbocycle or on the aliphatic part can be observed. Methylations can occur on phenolic oxygens and on the amine, leading to catecholamines (adrenaline, noradrenaline, dopamine). Arylethylamines are also usual to react with endogenous aldehydes through Pictet-Spengler reactions [25], leading to important biosynthetic intermediates (Scheme 1.7) like ... 

Phenylalanine- and Tyrosine-Derived Alkaloids. Carbohydrate metaboHsm leads via a seven-carbon sugar, ie, a heptulose, derivative to shikimic acid [138-59-0] (57), C H qO, which leads in turn to prephenic acid [126-49-8] (58), (43). 

There are only two groups of alkaloids that appear to be derived from tyrosine (25, R = OH) utilized as a Cg—C2 fragment and a Cg—Cj unit which comes from phenylalanine (25, R = H). The first is that small group found only in the Orchidaceae, exemplified by cryptostyline I [22324-79-4] (67, from Cryptostylisfulva Schltri) C29H22NO4. 

Table 9. Alkaloids Derived from Tyrosine as a Ce-C, Fragment and Phenylalanine as a Ce-C3 Fragment...

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... 

FACCHINI, D., DELUCA, V., Phloem-specific expression of tyrosine dopa decarboxylase genes and the biosynthesis of isoquinoline alkaloids in opium poppy, Plant Cell, 1995, 7, 1811-1821. 

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. 

An oxime derivative of indirubin (a natural bis-indole alkaloid used in traditional Chinese medicine to treat chronic myelocytic leukemia), indirubin-3 -monoxime (37), was found to be a potent inhibitor of cyclin-dependent kinases (CDKs), and of the proliferation of myeloid leukemia cells via inhibition of a tyrosine kinase . The 3D structure of the complex of 37 with CDK revealed that the oxime function is intact, and that it occupies the ATP-ribose site of the CDK-ATP structure. While the specific role of the oxime group in the biological activity of 37 is not clear, it was proposed that its reactivity may be utilized for further drug design... 

Figure 1. Contemporary scheme of morphine. Friedrich Sertiirner, who first isolated this alkaloid in an impure form in 1805, did know that it was converted from the pathway of tyrosine, Tyr. The correct morphine structure was determined by Gulland and Robinson in 1923. Moreover, even 200 years after Sertiirner s isolation, scientists are still discussing the synthesis of this alkaloid from a molecular point of view. This is a good example of the scientific evolution of knowledge of alkaloids.

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. 

Protoalkaloids are compounds, in which the N atom derived from an amino acid is not a part of the heterocyclic. Such kinds of alkaloid include compounds derived from L-tyrosine and L-tryptophan (see Table 1). Protoalkaloids are those... 

Figure 4. An example of a true alkaloid. L-tyrosine-derived alkaloid usambarensine has strong anti-malarial potential. Usambarensine was extracted from the root bark of African Strychnos usambaremis, a small tree in East and South Africa, and a small bush in West Africa.

Figure 5. An example of protoalkaloids. Mescaline is the alkaloid derived from L-tyrosine and extracted from the Peyote cactns (Lophophora williamsii) belonging to the Cactns family (Cactaceae). MescaUne has strong psychoactive and haUncinogenic properties. Peyote cactns grows in the desert areas of northern Mexico and the sonthern parts of the USA. This plant was nsed in Pre-Colnmhian America in the shamanic practice of local tribes.

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

The Lily botanical family (Liliaceae Adans., Juss.) (Table 14) is spread worldwide and contains more than 200 genera and around 3500 species. Some genera of this family produce L-tyrosine-derived alkaloids. The genus Kreysigia yields autumnaline, floramultine and kreysigine. 

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... 

L-tyrosine Tyrosine-derived alkaloids Indole alkaloids Quinoline alkaloids /3-carboline alkaloids Pyrroloindole alkaloids Ergot alkaloids Iboga alkaloids Corynanthe alkaloids Aspidosperma alkaloids Protoalkaloids Terpenoid indole alkaloids True alkaloids... 

Figure 31. Nuclei supplied to alkaloids by L-tyrosine in the synthesizing process.

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