Tyrosine-derived alkaloids

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

The second synthesis pathway from L-tyrosine is to dopamine across hydrox-ylation patterns and PLP activity. Dopamine is a very important compound in the 

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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). 

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.

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. 

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... 

Tyrosine-derived metabolites in this section do not include spiro-cyclohexadienyl-isoxazolines and related compounds (Sect. 3.22.3.3) or bastadins (Sect. 3.22.3.4), but they do include tyrosine-derived alkaloids that were covered in the Alkaloids section in the first survey (1). The prolific bryozoan Amathia convoluta, collected in Tasmania, has yielded amathamide G (1953) (1814), the latest of several amath-amide alkaloids from the genus Amathia (1). A Florida collection of this animal furnished the new convolutamines A-E (1954—1958) (1815), F (1959), and G (1960) (1425), and a Tasmanian sample of this bryozoan afforded convolutamine H (1961) (1319). A study of Amathia convoluta from the North Carolina coast has yielded volutamides A-E (1962-1966) (1816). Volutamides B and C reduce feeding by the pinfish (Lagodon rhomboids) and the urchin (Arbacia punctulata), respectively, and volutamides B and D are toxic toward larvae of the hydroid Eudendrium carneum. The New Zealand Amathia wilsoni contains the six novel amathaspiramides A-F (1967-1972) (1817). 

L-tyrosine-derived alkaloids also occur in the Berberry botanical family (Berberidaceae Torr., Gray, Juss.) (Table 1.12). Berberine is produced... 

Keywords antibacterial, biological activity, cytotoxic, marine brominated alkaloids, marine natural products, nematocidal, organohalogens, pharmaceuticals, tyrosine derived alkaloids... 

Respiratory center paralysis, stimulation after cardiac conduction failure, paralysis of the circulatory system, and perception efiects and paralysis of motor nerves are the demonstrated biological activities of the aconitine-type alkaloids in animal models. As for cardiotonic substances, other than higenamine, corynerine was also isolated and these alkaloids were described in Chapter 1 (phenylalanine- and tyrosine-derived alkaloids). 

Secondary metabolites are produced by plants in response to biotic or abiotic interactions with their environment and confer protection through a variety of antimicrobial, pesticidal, and pharmacological properties. Alkaloids are a class of plant secondary metabolites that traditionally have been classified as basic compounds derived firom amino acids that contain one or more heterocyclic nitrogen atom. About 20 % of plant species accumulate alkaloids, which are mostly derived from amino acids, e.g., phenylalanine, tyrosine, tryptophan, and lysine. The alkaloids are popular for their medicinal importance. The pharmaceutically important representatives of secondary metabolites are mostly alkaloids derived from tyrosine. In this chapter, we summarized the prior information, basic knowledge about the alkaloids, origin, physicochemical properties, uses, classification, biosynthetic reactions, and distribution of tyrosine-derived alkaloids especially opium alkaloids and their biosynthetic pathways in plants. We have also reviewed different web resources related to alkaloids and secondary metabolic pathway databases such as KEGG. 

In this chapter, we studied and analyzed the various biosynthetic routes involved in biosynthesis of alkaloids especially tyrosine-derived alkaloids. The plant alkaloids have been known to have important medicinal values and provided the medicines for the treatments of cancer, malaria, tuberculosis, etc. Keeping in mind the therapeutic importance, there is an urgent need to investigate their biosynthesis at the level of enzyme and gene. 

Figure 1.19. Tyrosine-derived alkaloids in the Rhoeadales, Berberidales, and Ranales. The first compound synthesized is norlaudanosoline, and nine distinct types of alkaloids are encountered either in restricted taxa or widely distributed A—salutaridine B— morphine pathway restricted to Papaver section Mecones C—isothebaine pathway, characteristic of Papaver section Macrantha D—Papaver section Miltantha E—Papaver section Scapiflora F-encountered in Chelidonium (Papaveraceae-Rhoeadales) and Berberis G—characteristic for Papaver section Orthoroedes, the Corydalis dicentra and Chelidonium spp. H—cryptowoline I—Papaver section Scapiflora, genus Escholtzia, and Argemone J—Papaver sections Orthoroedes and Pilosa, Data are compiled from publications by Stermitz (1968, 1974), Santavy (1966), Santavy et al. (1965, 1966) Slavik (1955), Slavik et al. (1963), Pfeifer (1962), and Tetenyi and co-workers (1961, 1965, 1967, 1968), Bandoni, et al. (1972, 1975). The reaction pathways are according to Barton and Widdowson (1972). Only pathways A, B, and C are shown in detail the others are only suggestions. The pathways leading to the dimeric (bis) alkaloids are not shown.

SCHEME 1.7 Tyrosine-derived alkaloid biosynthetic pathways (double head arrows figure bond cleavages during biosynthetic processes). 

This chapter is dedicated to Prof. Tomas Hudlicky, on the occasion of his 65th birthday in recognition of his synthetic contributions to tyrosine-derived alkaloids, and on a more personal note ( U.R.), in appreciation for his friendship and support. 

The main focus of this chapter rests on the discussion of biosynthetic rontes and biomimetic synthesis. Detailed information on (he enzymatic mechanisms is omitted. Also, the huge amount of research resnlts and scientific contributions available on tyrosine-derived alkaloids does not allow an in-depth coverage of the field. References to book chapters, review articles, and research papers are inclnded for further literature study. 

The following section provides an overview of the most important biosynthetic routes leading to prominent tyrosine-derived alkaloids. Throughout the chapter, alkaloids are categorized as outlined in Figure 12.1. A schematic overview of the biosynthetic routes described herein concludes this section. Names of enzymes that have been identified to catalyze specific reactions are included in the reaction schemes. 

The manifold possibilities for the elaboration of structurally intriguing natural products via the aforementioned oxidative aryl-aryl coupling reactions emphasize the importance of phenolic coupling reactions in the biosynthesis of tyrosine-derived alkaloids. This important reaction not only plays a significant role in the biosynthesis of benzyltetrahydroisoquinoline alkaloids but also for the construction of phenethylisoquinoline alkaloids and Amaryllidaceae constituents, discussed in the following sections. 

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