Alkaloids derived from nicotinic acid

Tobacco Alkaloids. The relatively small number of alkaloids derived from nicotinic acid (27) (the tobacco alkaloids) are obtained from plants of significant commercial value and have been extensively studied. They are distinguished from the bases derived from ornithine (23) and, in particular, lysine (24), since the six-membered aromatic substituted pyridine nucleus common to these bases apparendy is not derived from (24). 

Figure 29. The nucleus of alkaloids derived from nicotinic acid.

Alkaloids derived from nicotinic acid contain a pyridine nucleus. Nicotinic acid itself is synthesized from L-tryptophan via A-formylkynurenine, L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid. 

The other alkaloids derived from nicotinic acid, with pyridine nucleus such as arecoline, arecaidine and guvacoline, are tetrahydronicotinic acid (guvacine) derivatives. 

GROSS, D., Alkaloids derived from nicotinic acid, in Biochemistry of Alkaloids, (K. Mothes, H.-R. Schiitte and M. Luckner, eds.), VCH, Weinheim. 1085, pp. 163-187. 

Plants produce various pyridine alkaloids derived from nicotinic acid. Trigonelline, the major component in coffee seeds, and ricinine, the toxic alkaloid produced by Ricinus communis, are formed from nicotinic acid originating from the NAD catabolism [20, 25, 26], Quinolinic acid was found to be an efficient precursor in the biosynthesis of nicotine [27]. 

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. 

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. 

The tobacco alkaloids, especially nicotine, are derived from nicotinic acid (see page 311) but also contain a pyrrolidine ring system derived from ornithine as a portion of their structure. 

The rather similar alkaloids anabasine and anatabine come from different biosynthetic pathways. Labelling experiments outlined below show the origin of one carbon atom from lysine and others from nicotinic acid. Suggest detailed pathways. (Hint. Nicotinic acid and the intermediate yoi have been using in Problem 3 in the biosynthesis of the piperidine alkaloid are both electrophilic at position 2. You also need an intermediate derived from nicotinic acid which is nucleophilic at position 3. The biosynthesis involves reduction.)... 

The alkaloids anabasine (86) and sedamine (87) are typical representatives of one such alkaloid family past results suggest that they are both formed by condensation of a suitable nucleophile with a unit of A piperideine (85) derived from lysine (Scheme 15). The nucleophile is possibly benzoylacetic acid for sedamine49 and has been shown to be derived from nicotinic acid for anabasine.50 The origin of the different side-chains will be discussed in detail later under the individual alkaloids. For the moment this account will focus on the pattern of incorporation of lysine and will try to correlate the results from different systems. 

Most remarkable for proving that structural relationships are not always what they seem are anatabine [(34) p. 11] and dioscorine (8). Inspection and experience with other piperidine alkaloids leads one to expect a biosynthesis for the piperidine ring [heavy bonding in (8)] from lysine via A -piperideine (3). However, in both cases it turns out that this ring derives from nicotinic acid [the exceptional derivation of the piperidine nuclei of coniine and pinidine (9) from acetate has been known for some time ]. 

Ricinine.—Ricinine (49), the alkaloid of castor bean plants, is derived from nicotinic acid (28) and quinolinic acid (48), and its formation is intimately associated with the pyridine nucleotide cycle cf. ref. 6. Quinolinic acid is built from a C3 fragment that is formed from glycerol via glyceraldehyde and a C4 unit that is related to succinic or aspartic acids. A recent investigation has confirmed this pathway for ricinine (49) and indicated that dihydroxyacetone phosphate lies between glycerol and glyceraldehyde (loss of tritium from C-2 of labelled glycerol). ... 

True alkaloids derive from amino acid and 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 is a brown liquid. True alkaloids... 

Nicotinic acid (Figure 2.9) provides alkaloids with the pyridine nucleus in the synthesizing process. This nucleus appears in such alkaloids as anaba-sine, anatabine, nicotine, nornicotine, ricine, and arecoline. Moreover, many alkaloids contain the pyridine nucleus as part of their total skeleton. For example, anabasine is derived from nicotinic acid and lysine.Alkaloids with the pyridine nucleus occur in such plants as tobacco (Nicotiana... 

Nicotine was isolated by Posselt and Reimann in 1828 [1], and subsequently the chemical structure was clarified [2-4]. As described later, the pyridine ring of nicotine is derived from nicotinic acid, which is biosynthesized from aspartic acid. Therefore, nicotine can also be described as an alkaloid derived from aspartic acid. On the other hand, the pyrroHdine ring is biosynthesized from ornithine.When DL-[5- C]-pyrroline-5-carboxyhc acid, a postulated biosynthetic precursor derived from ornithine, was incorporated into Nicotiana mstica, the incorporated rate (0.04%) was very low, and the 2 - and 5 -positions were equally labeled with (F ure). Consequently, it was estimated that the biosynthetic intermediate was not this compound but another symmetrical structure [5]. 

Simple examples of alkaloids that contain a nicotinic acid residue as a partial structure include nicotine and anabasine. These alkaloids also possess a pyrrolidine and a piperidine ring in their partial structure, respectively, in addition to the pyridine ring derived from nicotinic acid.The origins of the aliphatic portions of these alkaloids are ornithine and lysine, respectively. In this volume, these particular alkaloids are described in the sections on ornithine-derived and lysine-derived alkaloids, respectively. 

Nicotine is the main alkaloid of tobacco Nicotiana tabacum) of the Solana-ceae. Anabasine is the main alkaloid of Anabasis aphylla (Chenopodiaceae), although trace amounts are also present in tobacco. Both nicotine and anabasine possess strong insecticidal activity. The structures of these alkaloids also have similarities in that one contains a pyrrolidine ring derived from ornithine and the other a piperidine ring derived from lysine, both of which are joined at C-3 of the pyridine ring, itself derived from nicotinic acid [1]. These alkaloids were described in detail in Chapters 3 and 4 on ornithine-and lysine-derived alkaloids, respectively. The procedure for the formation of nicotine and anabasine by condensation of A -pyrrolidine and A -piperidine with a nicotinic acid moiety is shown in the figure [2]. 

It was shown that nicotinamide was derived from nicotinic acid, and that nicotinic acid was biosynthesized from aspartic acid and glycerol, as described at the beginning of this chapter. Therefore, ricinine, as in the case of arecoline and nicotinic acid, is also an alkaloid derived from aspartic acid. 

Alkaloids that possess an aromatic pyridine ring often are called pyridine alkaloids (Leete, 1980 Pinder, 1993 Strunz and Findlay, 1985) approximately 250 alkaloids of this type are known (Verpoorte et al., 1991). Although many are derived from nicotinic acid (Fig. 28.18), others arise from aro-matization of piperidine alkaloids and other pathways (Waller and Nowacki, 1978). This chapter includes several of the most important compounds of this type, although others (such as a number of monoterpene-derived alkaloids, Nu-phar alkaloids, and sesquiterpene alkaloids of the Celastra-ceae) are discussed in Chapter 36. 

A series of compounds that appear to be derived from nicotinic acid is found in a number of euphorbiaceous plants. Ricinine (49), an alkaloid from Ricinus communis, is derived from nicotinic acid via nicotinamide (50). This alkaloid may occur in quantities as great as 1% of the plant dry weight. A crude enzyme preparation has been isolated that will convert a series of pyridinium salts into ricinine and related compounds (Fig. 28.20) (Fodor and Colasanti, 1985). This alkaloid disappears completely from senescent leaves. Ricinine (49) has an LD50 p.o. of 42 mg/kg in Agelaius (Wink, 1993). 

A series of alkaloids have been isolated from members of the genus Dioscorea (Dioscoreaceae). These compounds are derived from nicotinic acid and compound 53 appears... 

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