Arginine-derived alkaloids

Protein amino acids L-alanine L-arginine Arginine-derived alkaloids True alkaloids... 

Arecoline 40, 71, 86, 208, 209 Arginine-derived alkaloids 62 Aromatic alkaloids 10 Arosine 22 Arthropod alkaloids 6 Arundacine 8, 38 Arundamine 8, 38 Aspidoalbine 16, 38 Aspidolimidin 16, 68 Aspidolimidine 16... 

Alkaloids derived from ornithine, arginine Pyrrolizidine alkaloids Miscellaneous alkaloids X X X X X ... 

As will be described later, ornithine is an amino acid that is biosynthetically derived from arginine. Consequently, alkaloids derived from these amino acids are combined and described in this chapter. 

L-Cysteine derivatives Ii-Arginine derivatives Isoquinoline alkaloids... 

In plants, this non-protein amino acid is derived from L-glutamate and in animals from L-arginine. Moreover, Figure 23 demonstrates that synthesis of alkaloids is complicated by the ability of the same amino acid to synthesize many different alkaloids. 

There are several classes of alkaloids. Among these are purines such as xanthine and caffeine, ter-penes (Chapter 22), polyketides (Chapter 21), and alkaloids derived from amino acids. The basic amino acids ornithine, arginine, histidine, and lysine as well as the aromatic amino acids, anthranilate, and nicoti-nate are some of the starting materials.199 201 Robinson202 203 in 1917 recognized that many alkaloids are derived directly from aromatic amino acids. He proposed that alkaloids arise from Mannich reactions (Eq. 25-12) in which an amine and an aldehyde (probably through a Schiff base) react with a nucleophilic carbon such as that of an enolate anion. Many of the... 

The nitrogen content of honey is low and varies widely, with an average of about 0.04%. This consists mainly of alkaloids, chlorophyll derivatives, amino acids, and amines (Al-Mamary et al., 2002). Of amino acids, proline is dominant, but arginine, tryptophan, and cysteine, whose presence is characteristic of some types of honey, have also been detected (Anklam, 1998). Analysis of the amino acid profile has greater potential in detecting the geographic and botanic origin of honey than the protein composition (Anklam, 1998). 

The majority of alkaloids have been found to be derived from amino acids, such as tyrosine, phenylalanine, anthranilic acid, tryptophan/tryptamine, ornithine/arginine, lysine, histidine and nicotinic acid (Fig. 2.1). However, alkaloids maybe derived from other precursors such as purines in case of caffeine, terpenoids, which become aminated after the main skeleton has been synthesized i.e. aconitine or the steroidal alkaloids, are found in the Solanaceae and Liliaceae. Alkaloids may also be formed from acetate-derived polyketides, where the amino nitrogen is introduced as in the hemlock alkaloid, coniine. 

Both alkaloids have (+) and (-) forms but only the (-) hyoscyamine and (-) scopolamine are active. The biosynthetic pathway of tropane alkaloids, Fig. (1) is not totally understood, especially at the enzymatic level. Edward Leete has pioneered the biosynthetic studies of tropane alkaloid since 1950"s using whole plants and isotope labels [85-86]. The tropane alkaloid hyoscyamine is bioconverted by the enzyme H6H (hyoscyamine 6p-hydroxylase, EC 1.14.11.11) to scopolamine via 6p-hydroxyhyoscyamine. Hyoscyamine is the ester of tropine and (S)-tropic acid. The (S)-tropic acid moiety derives from the amino acid L-phenylalanine, while the bicyclic tropane ring derives from L-omithine primarily or L-arginine via tropinone. Tropinone is stereospecifically reduced to form either, tropine which is incorporated into hyoscyamine, or on the other hand into pseudotropine which proceeds to calystegines, a group of nortropane derivates that were first found in the Convolvulaceae family [87]. 

Saxitoxin (120), a paralytic shellfish poisoning alkaloid, was obtained from cultures of a red tide dinoflagellate Alexandrium sp. The toxin is also used for studies on ion channels. The biosynthesis of saxitoxin (120) involves arginine as a precursor of the guanidinio groups, whereas the perhydropurine skeleton is derived from Claisen condensation of acetate with arginine. The carbon atom in the side chain is derived from Y-adenosyl methionine. " ... 

The evidence available at the present time suggests that the nitrogen of Z-hyoscyamine and its allies may be derived from the 6-amino group of arginine and ornithine. Of the further stages of the conversion and of the sources of the other parts of the alkaloid molecule, nothing certain is yet known. 

Most pyrrolizidine alkaloids are esters of basic alcohols known as necine bases. The most frequently studied pyrrolizidine alkaloids are formed from the polyamines, putrescine and spermidine, and possess one of three common necine bases retronecine, heliotridine, and otonecine. Putrescine is utilized exclusively as a substrate in secondary metabolism, whereas spermidine is a universal cell-growth factor involved in many physiological processes in eukaryotes. Spermidine biosynthesis begins with the decarboxylation of SAM by SAM decarboxylase 165). The aminopropyl group is then transferred from decarboxylated SAM to putrescine by spermidine synthase to form spermidine (Scheme 5). Putrescine can be produced from ornithine by ODC. However, putrescine is derived from the arginine-agmatine pathway in pyrrolizidine alkaloid-producing plants due to the absence of ODC activity 166). 

Nicotine and anabasine are considered to be alkaloids derived firom nicotinic acid (pyridine-3-carboxylic acid).These alkaloids can be also classified as derived from ornithine and lysine, respectively. Therefore, these alkaloids are described in Chapter 10.1 (as alkaloids derived from nicotinic acid), in Chapter 3.1 (alkaloids derived from ornithine and arginine), and in Chapter 4.3 (alkaloids derived from lysine). However, such exceptions are relatively rare if the classification of alkaloids is conducted based on their biosynthetic origin. 

Also, in this chapter, the polyamine alkaloids, such as ephedradine and kukoamine, which contain a polyamine unit derived from putrescine and are biosynthesized by decarboxylation of ornithine, will be discussed. Furthermore, atropine and cocaine, which are biosynthesized via the AT-methyl-l-pyrrolinium ion and formed by methylation of putrescine followed by cyclization, and tetrodotoxin, which was once considered to be biosynthesized from arginine, will be discussed. 

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