Histidine alkaloids derived from

Histamine is obtained by the decarboxylation of histidine. It is distributed in the tissues and blood, and is also produced by fermentation through the activity of microorganisms. Because histamine is produced by decarboxylation of histidine, it can be regarded as one of the simplest alkaloids derived from histidine. 

Only a very limited number of alkaloids derived from histidine are known. As an example of these alkaloids, (+)-pilocarpine is described in this chapter, as well as histamine. Alkaloids derived from histidine are also called imidazole alkaloids because of the imidazole nucleus in the histidine skeleton. 

Several alkaloids derived from histidine occur in plants. Probably the best known of these is pilocarpine (5), found in species of Pilocarpus (Rutaceae) (Fig. 37.2). This compound is a peripheral stimulant of the parasympathetic system and is used topically as a myotic to counteract the mydriatic effects of atropine and other parasympatholytic drugs. Pilocarpine is used for the treatment of glaucoma (as a 0.5-10% solution). 

Fodor, G. B. Alkaloids derived from histidine and other precursors. In Encyclopedia of Plant Physiology, New Series, Vol. 8, Secondary Plant Products (E. A. Bell, B. V. Charlwood, eds.), pp. 160-166. Springer, Berlin-Heidelberg-New York 1980... 

Alkaloids Derived from Histidine Imidazole C (Pilocarpine, Pilosine)... 

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. 

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... 

Fig. 46 Some alkaloids derived from acetate and histidine.

Figure 1.6a. Structures of some Rutaceae alkaloids. This order is recognized for accumulating alkaloids derived from different biosynthetic pathways, e.g., from anthranilic acid, tyrosine, tryptophan, and histidine.

It has been suggested that these alkaloids apparently are derived biogene-tically from histidine (77, p. 840), but biosynthetic evidence still has to be forthcoming. 

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. 

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