Purine alkaloids, caffeine

The major pharmacological constituents of tea are the purine alkaloids caffeine (2.9-4.2%), theobromine (0.15-0.2%), and theophylline (0.02-0.04%). Also present are triterpene saponins (including barringtogenol C and Rl-barringenol), catechins (theaflavine, theaflavin acid, thearubigine), and caffeic acid derivatives (chlorogenic acid and theogallin). A cup of brewed tea contains approximately 20-100 mg of caffeine... 

During imbibition of whole tea seeds (6 days) two purine alkaloids, caffeine and theobromine, did not decrease in the seed coats and there was no increase in the seeds. In parallel with and after the breaking seed coats there was a gradual release of caffeine from coats of germinating seeds. By contrast, when the seed was freed from the outer seed coat and soaked, imbibition of the seed required only two days and simultaneously caffeine was released from the inner seed coat. 

Purine alkaloids Caffeine synthase Camellia sinensis, Coffea arabica... 

The purine alkaloids caffeine, theobromine, and theophylline (Figure 6.135) are all methyl derivatives of xanthine and they commonly co-occur in a particular plant. The major sources of these compounds are the beverage materials such as tea, coffee, cocoa, and cola, which owe their stimulant properties to these water-soluble alkaloids. They competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP and subsequent release of adrenaline. This leads to a stimulation of the CNS, a relaxation of bronchial smooth muscle, and induction of diuresis, as major effects. These effects vary in the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine. 

There is less information in the literature about binding of alkaloids to ribonucleic acid than there is for deoxyribonucleic acid but such binding does occur. However, since ribonucleic acid is single-stranded, the intercalation mechanism does not apply. Binding of the purine alkaloids caffeine and theophylline follows the reverse order from their binding to DNA — theopylline binds with 10,000 times the affinity of caffeine [345], Elliptinium acetate, best-known for its intercalation into DNA, is easily oxidized to an A-ring quinone amine that binds to the 2 -oxygen atom of ribose units in RNA. The first product then cyclizes to a spiro derivative [346]. 

Scheme 4. Biosynthesis of the purine alkaloids caffeine and theobromine. Molecular clones have been isolated for all enzymes shown. Abbreviations CS, caffeine synthase MXN, 7-methyIxanthosine nucleosidase MXS, 7-methyIxanthosine synthase.

Similar to polyphenols, alkaloids are products of the secondary metabolism of plants, which have been identified in hundreds of plant species with great structural diversity [21], Methybcanthines derived from purine nucleotides are known collectively as purine alkaloids. Caffeine, theophylline, and theobromine alkaloids are methylated xanthine derivatives. Figure 14.2 shows their chemical structures and, as can be observed, these structures differ only in the number and the position of one methyl substituent and/or hydrogen atom around the xanthine ring system. 

Fig,l Structures of the purine alkaloids caffeine, theobromine, theophylline, and paraxanthine... 

The purine alkaloid caffeine (1,3,7-trimethylxanthine) was discovered in coffee Coffea arahka) and tea (Camellia sinensis) in the 1820s (Ashihara and Crozier 2001) (Figures 4.10 and 4.11). Theobromine is also a commercially important purine alkaloid found in the seeds of cacao (Theobroma cacao). Three groups of plants that accumulate purine alkaloids... 

Ai,A/-bis(hydroxymethyl) formamide [6921-98-8] (21), which in solution is in equiUbrium with the monomethylol derivative [13052-19-2] and formaldehyde. With ben2aldehyde in the presence of pyridine, formamide condenses to yield ben2yhdene bisformamide [14328-12-2]. Similar reactions occur with ketones, which, however, requite more drastic reaction conditions. Formamide is a valuable reagent in the synthesis of heterocycHc compounds. Synthetic routes to various types of compounds like imida2oles, oxa2oles, pyrimidines, tria2ines, xanthines, and even complex purine alkaloids, eg, theophylline [58-55-9] theobromine [83-67-0], and caffeine [58-08-2], have been devised (22). 

Foods derived from cocoa beans have been consumed by humans since at least 460 to 480 AD. The source of cocoa beans, the species Theobroma, contains a variety of biologically active components. These include the purine alkaloids theobromine, caffeine, and theophylline. Structurally, they are methylated xanthines and, thus, are often referred to as methylxanthines. Theobromine (3, 7-dimethylxanthine) is the predominant purine alkaloid in cocoa and chocolate. Caffeine (1, 3, 7-trimethylxanthine), the major purine alkaloid found in coffee and tea, is found in cocoa and chocolate at about one eighth the concentration of theobromine. Only trace amounts of theophylline (1, 3-dimethylxanthine) are detected in cocoa and chocolate products. 

Caffeine in tea and coffee inhibits the phosphodiesterase that degrades cAMP. The resultant increase in cAMP levels, therefore, mimics the action of mediators such as the catecholamines that modulate adenylate cyclase. Caffeine and the related theophylline (both purine alkaloids, see Box 11.12) are thus effective stimulants of the CNS. 

In contrast with the seed caffeine of Coffea species, relatively little attention has been paid to that of tea. This is in part because the fruit of tea, including the seeds, is of minor economic importance compared with that of coffee moreover earlier studies revealed little caffeine in the tea seed (13.141. Recently we (H) found that the pericarp contains the greatest concentrations of alkaloids in the dry fruit of tea, and that appreciable amounts occur in the seeds, especially in the coats. Thus, from physiological and ecological viewpoints, our concerns are the roles of purine alkaloids and seed coats of tea during fruit development (seed formation) and seed germination. Caffeine in Coffea arabica seed is synthesized in the pericarp, transported to the seed, and accumulated there during fruit... 

Purine alkaloids Rubiaceae Cojfea arabica Caffeine Theophylline Theobromine... 

The Coffee (syn. Madder) botanical family (Rubiaceae Juss.) (Table 15) consists of more than 400 genera and over 6000 species. It grows in the tropics and the sub-tropics. Plants belonging to this family include trees, bushes and liane. The Coffee plant family contains two major purines of adenine- /guanine-derived alkaloids, the so-called purine alkaloids . Purine is a nitrogenous base of nucleotide, which consists of just purine and pentose sugar (o-ribose or 2 deoxy-D-ribose). Typical purine alkaloids are caffeine, theophylline and theobromine. The same or similar purine alkaloids occur also in other plant families. 

Issandou-Carles. Action of purine alkaloids and caffeine-containing drugs on hyaluronidase. C R Seances Soc Biol Ses Fil 1954 148 1075. CS002 Renold, W., R. Naf-Muller, U. Keller,... 

Caffeine Caffeine [l,3,7-trimethyl-l//-purine-2,6(3/7,7//)-dione], molecular formula C8H10N4O2, is a xanthine (purine) alkaloid, found mainly in tea leaves Camellia sinensis) and coffee beans (Coffea arabica). Caffeine is sometimes called guaranine when found in guarana (Paullinia cupana), mateine when found in mate (Ilex paraguariensis) and theine when found in tea. Caffeine is found in a number of other plants, where it acts as a natural pesticide. It is odourless white needles or powder. Apart from its presence in the tea and coffee that we drink regularly, caffeine is also an ingredient of a number of soft drinks. 

Caffeine and other purine derivatives can be detected by the Murexide test. In this test the alkaloids are mixed with a tiny amount of potassium chlorate and a drop of hydrochloric acid and evaporated to dryness, and the resulting residue is exposed to ammonia vapour. Purine alkaloids produce pink colour in this test. 

Part of herb used The seeds, which are purple-brown to black with a characteristic white eye , contained within a red-orange fruit about the size of a hazelnut. Main actives Guarana has the highest known caffeine content of any herb at 3.6-5.8%. It also contains small amounts of theophylline and theobromine, the other stimulant purine alkaloids similar to caffeine. Besides these, guarana contains about 12% tannins and some saponins. 

Main actives Purine alkaloids - mainly caffeine (0.6-3.7%) with some theophylline and theobromine, tannins, proanthocyanidins and 45% starch. 

The purine derivatives caffeine, theobromine, and theophylline (Figure 6.135) are usually referred to as purine alkaloids. As alkaloids they have a limited distribution, but their origins are very closely linked with those of the purine bases adenine and guanine, fundamental components of nucleosides, nucleotides, and the nucleic acids. Caffeine, in the form of beverages such as tea, coffee, and cola is one of the most widely consumed and socially accepted natural stimulants. It is also used medicinally, but theophylline is... 

ASHIHARA, H., GILLIES, F.M., CROZIER, A., Metabolism of caffeine and related purine alkaloids in leaves of tea (Camillia sinensis L.) Plant Cell Physiol, 1997,38,413-419. 

Caffeine (Fig. 11.3), widely used by humans as a stimulatory drug, has so far been detected only in a few plant species. The biological roles of caffeine are believed to be in defense against herbivory or as an allelopathic response to potential competitors.83 Caffeine is derived from the purine alkaloid xanthosine. From xanthosine, three methylations are necessary to produce caffeine. First, xanthosine is methylated on N7 by 7-methylxanthosine synthase (MXS or 7NMT) to produce 7-methylxanthosine, which is enzymatically hydrolyzed to produce 7-methylxanthine and ribose.85,86 The methylations of N1 and N3 of 7-methylxanthine to produce 1,3,7-trimethylxanthine (caffeine) occur in young leaves of tea, and the same enzyme, caffeine synthase, apparently catalyzes both reactions.55 In coffee plants, caffeine is mainly found in the beans but also occurs in the leaves. Caffeine is stored in the vacuoles of coffee leaves as a complex with polyphenols such as chlorogenic acid.87 In contrast to tea, coffee plants appear to have separate enzymes for each step of N-methylation.57... 

WALDHAUSER, S. S. M., BAUMANN, T. W., Compartmentation of caffeine and related purine alkaloids depends exclusively on the physical chemistry of their vacuolar complex formation with chlorogenic acids., Phytochemistry., 1996, 42, 985-996. 

Caffeine and related purine alkaloids (AA) papaverine (AA) chelerythrine, sanguinarine, and related benzophenanthridine alkaloids (AA) colchicines (AA) infractine and related indole alkaloids (AA)... 

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