Histamine alkaloids derivation from

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. 

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. 

This chapter will cover the alkaloids containing the imidazole nucleus which is the smallest group of alkaloids in terms of number of compounds known. This class of alkaloids is synthesized by precursors derived directly from the amino acid, L-histidine. The known structures can be divided in those derived from histamine as a precursor and the other ones called Pilocarpus alkaloids that... 

The simplest histamine derivative from this group, A/ -acetyIhistamine (7), was firstly identified by Appel and Werle in S. oleracea [7] crude alkaloid extract. 

Biogenic amines are a group of aliphatic, aromatic or heterocychc bases derived from amino acids, which exhibit a variety of biological effects, as they perform different functions in animal and plant tissues. Some biogenic amines are building materials for the biosynthesis of phytohormones of the auxin group, plant protoalkaloids (such as hordenine and gramine), true alkaloids and other secondary plant metabolites. In animal tissues they have the function of tissue hormones (e.g. histamine) and are precursors of adrenal hormones (catecholamines). 

Venoms from the fire ants Solenopsis invicta and 5. geminata are free of detectable histamine but possess histamine-release activity. This activity can account for the edema, itch, redness, warmth, and possibly the pain and burning sensations resulting from fire ant stings. And it can be attributed to the piperidines which constitute the major component of the venom. It has actually been proved that 6-methyl-2-n-undecylpiperidines (Ic and Id), components of S. geminata, possess the histamine-release activity (75). Due to some of the above-mentioned various activities the piperidine alkaloids play roles as defensive compounds. In addition to 2-alkyl-6-methylpiperidines, their N-methyl derivatives (3) are found in S. pergandei, S. carolinensis, and S. conjurata, and 1-piperideine derivatives (6 and 7) in S. sp. A (Puerto Rico) and S. xyloni (Table I). 

Histamine possesses hormone activity in animals (E 3.1) and acts as a neurotransmitter (E 3.2). It is a plant feeding deterrent present, for instance, in nettle toxin (E 5.5.3). Also the alkaloid pilocarpine has strong physiological activity in vertebrates and deters potential predators (E 5.5.3). It is used as a cholinergic drug in medicine (F 2). Urocanic acid, hydantoin propionic acid, imidazoleacetic acid riboside, 1-methylhistidine, 1-methylimidazoleacetic acid and other imidazole derivatives are involved in the removal of L-histidine and histamine residues from the organism of animals. They are found in the urine. Urocanic acid is also a constituent of sweat (E 1). It is involved in the protection of skin to UV radiation (E 2.2). 

In this chapter, we will only discuss about nonmarine alkaloids which are originated directly from histidine and are not simple peptide alkaloids. The alkaloids here discussed were classified, accordingly to their biosynthetic origin, in simple histamine derivatives and the so-called Pilocarpus alkaloids which are originated directly from histidine but from different precursors. 

Other examples of histamine amides that also contain a lactam portion are the alkaloids from Cynometra spp. (Fabaceae). Strucmrally, they are very similar to that one found in Pilocarpus species. C. hankei Harms, C. ananta Hutch. Dalziel, and C. lujae De Wild, and are indigenous to west tropical Africa, which contain lactams derivatives, in which occur isomerization at imidazole ring level, such as anantine(16)/isoanantine (19) and cynodine (18)/isocynodine (19) [22]. As these alkaloids are only found in Cynometra species, possibly, they have a chemotaxo-nomic importance to this genus. 

Imidazole natural products, especially those derived bio-synthetically from histidine, make up a small portion of the alkaloids found in nature. The majority of these alkaloids are thought to be produced from two histidine metabolites (1) histamine (11), which results from histidine decarboxylase-catalyzed decarboxylation [14], and (2) urocanic acid (12),... 

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