Xanthine alkaloids caffeine

The dominating active ingredients in the three plants are xanthine alkaloids caffeine, theobromine and theophylline (Fig. 2.36). Raw coffee contains 0.9-1.4% (Arabica) or 1.5-2.6% (Robusta) of caffeine. Tea leaves contain 3.2 % of caffeine, but the different preparation method results in about half as much caffeine in the drink compared to coffee. The main active ingredient of cocoa is theobromine, there is only 0.2% caffeine in it, but this small amount is still responsible for the stimulating effect. 

Many indigenous groups in the world have developed particular teas used as stimulant beverages. Among those are coffee, green tea, black tea, guarana, and mate. It is interesting to note that the xanthine alkaloid caffeine is a principal component of all these drinks. In this book, caffeine is described in Chapter 11.1. 

Their wide spectrum of biolc cal activities provides numerous classes of useful medicinal agents, and yet, at the same time, they provide a global paradox. In spite of many health beneficent effects, two alkaloids, cocaine and morphine (and its derivative heroin), are the ft)cus of a counter culture of illicit use of biological powerful alkaloids, and many alkaloids, because of their profound toxicity, are to be feared. On the other hand, the xanthine alkaloids, caffeine and threobromine, are an integral aspect of providing pleasure in the daily lives of most of the world in the consumption of tea, coffee, and chocolate. 

Abstract Caffeine, a xanthine alkaloid, occurs in teaplants, coffee, mate leaves and cola nuts, ft is also commonly found beverages, such as cola drinks, tea and energy drinks. 

Several purine derivatives are found in nature, e.g. xanthine, hypoxanthine and uric acid. The pharmacologically important (CNS-stimulant) xanthine alkaloids, e.g. caffeine, theobromine and theophylline, are found in tea leaves, coffee beans and coco. The actual biosynthesis of purines involves construction of a pyrimidine ring onto a pre-formed imidazole system. 

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 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. 

The major bases found in nucleic acids are adenine and guanine (purines) and uracil, cytosine, and thymine (pyrimidines). Thymine is found primarily in DNA, uracil in RNA, and the others in both DNA and RNA. Their structures, along with their chemical parent compounds, purine and pyrimidine, are shown in Figure 10.1, which also indicates other biologically important purines that are not components of nucleic acids. Hypoxanthine, orotic acid, and xanthine are biosynthetic and/or degradation intermediates of purine and pyrimidine bases, whereas xanthine derivatives—caffeine, theophylline, and theobromine—are alkaloids from plant sources. Caffeine is a component of coffee beans and tea, and its effects on metabolism are mentioned in Chapter 16. Theophylline is found in tea and is used therapeutically in asthma, because it is a smooth muscle relaxant. Theobromine is found in chocolate. It is a diuretic, heart stimulant, and vasodilator. 

The purine group of alkaloids includes the vegetable alkaloids caffeine, theobromine, theophylline and the animal alkaloids xanthine, hypoxanthine, guanine and adenine. The most common substance which is a purine compound is uric acid, but, though directly related to the alkaloids given above, it is not itself usually considered as an alkaloid. The constitution of uric acid has been fully considered (Part I, p. 442). It is the tri-hydroxy derivative of a substance known as purine which is the mother substance of the purine alkaloids also. 

Several authors have included one or more naturally occurring xanthine derivatives (caffeine, theobromine and theophylline) in their gas chromatographic separation of alkaloids. Lloyd et al.1 used a packed column with SE-30 on Chromosorb VI, so did Brochmann-Hanssen and... 

Caffeine enters the bloodstream about ten minutes after its ingestion and stays in the body for up to twelve hours. Like other alkaloids, caffeine has powerful physiological effects on humans and animals. It stimulates heart muscle and relaxes certain structures that contain smooth muscle, including the coronary arteries and the bronchi. It is a diuretic. Theophylline and theobromine, two other plant alkaloid derivatives of xanthine, have physiological effects similar to those of caffeine. 

Xanthates. See Carbonodithioates 9/f-Xanthene, 9-chloro-9-phenyl- pixyl O-protection with, 341-324 Xanthine = 3,7-dihydro-ltf-purine-2,6-dione synthesis and methylation, 306 Xanthine alkaloids pr., 290 caffeine, 306... 

Caffeine is the most popular psychoactive stimulant. This xanthine alkaloid occurs in coffee, tea, and cola beverages. At a modest dose of 100-200 mg, it enhances wakefulness and reduces fatigue. However, intake of higher quantities (>500 mg/day) can cause addiction. Other psychostimulant substances include deanol, pemoline, and their derivatives. These substances have limited clinical apphcation. The structures of caffeine. 

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. 

Fischer carried out extensive work on the chemistry of purine and on those compounds containing its nucleus. Purine is one of the two nitrogen base ring systems present in DNA. Fischer synthesized approximately 150 members of this class of heterocyclic compounds (including the first synthesis of the alkaloid caffeine (see Experiment [IIB]), uric add, and the xanthines (also see Experiment [IIB]). He developed a general s)mthesis of another nitrogen heterocyde, indole, which was so effective that it has become one of the classic synthetic methods of organic chemistry and is known today as the "Fischer indole synthesis" ... 

A Figure 7.2 Basic drugs and classes, the largest subgroup in the acid-base classification scheme. The alkaloids are (or at least once were) derived from plant matter, while nonalkaloids are generally synthetic or semisynthetic. Tropane alkaloids Include cocaine, while tryptamines include mescaline and psilocyn. Caffeine and theophylline are xanthine alkaloids. The selective serotonin reuptake inhibitors (SSRIs) include the second-generation SSRI antidepressants. Prozac (fluoxetine, shown) and Paxil belong to this class. 

A Figure 8.22 Representative xanthine alkaloids. Theophylline is found in many teas, in chocolate, and, occasionally, as an adulterant, although caffeine is much more common. 

Caffeine A xanthine alkaloid sometimes encoxmtered as an adulterant of heroin or related drug samples. Cahn-Ingold-Prelog convention The most common method used to describe bonding around a chiral atom uses the R/S notation and assigned priorities. 

Xanthine alkaloids Alkaloids that include caffeine, theophylline and other compounds found in coffee, tea, and chocolate. 

The history of the xanthine alkaloids (Fig. 4.38) goes back to ancient times when their plant sources were discovered. Caffeine was extracted from tea, coffee and cocoa theophylline was mainly found in tea extract,... 

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). 

For many years oral xanthines, shown in Table 2, were the preferred first-line treatment for asthma in the United States, and if the aerosol and oral formulations of P2" go sts are considered separately, as they are in Table 1, this was still the case in 1989. Within this class of compounds theophylline (8), or one of its various salt forms, such as aminophylline [317-34-0] (theophylline ethylenediamine 2 l), have been the predominant agents. Theophylline, 1,3-dimethylxanthine [58-55-9], is but one member of a class of naturally occurring alkaloids. Two more common alkaloids are theobromine (9), isomeric with theophylline and the principal alkaloid in cacao beans, and caffeine, (10), 1,3,7-Trimethylxanthine [58-08-2], found in coffee and tea. 

Xanthines such as caffeine (1)> theophylline (aminophylline) (2), and theobromine (3) are a class of alkaloids that occur in numerous plants. The CNS stimulant activity of aqueous infusions containing these compounds has been recognized since antiquity. This has, of course, led to widespread consumption of such well-known beverages as coffee (Coffea arabica), tea (Thea sinesis), mate, and cola beverages (in part Cola acuminata). The annual consumption of caffeine in the United States alone has been estimated to be in excess of a billion kilos. The pure compounds have found some use in the clinic as CNS stimulants. In addition, caffeine is widely used in conjunction with aspirin in various headache remedies. 

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. 

Three xanthines are pharmacologically important caffeine, theophylline, and theobromine. All three alkaloids, which occur naturally in certain plants, are widely consumed in the form of beverages (infusions or decoctions) derived from these plants. Coffee primarily contains caffeine (about 100-150 mg per average cup) tea contains caffeine (30-40 mg per cup) and theophylline and cocoa contains caffeine (15-18 mg per cup) and theobromine. Cola drinks also contain significant amounts of caffeine (about 40 mg/12 oz). The CNS stimulation associated with these beverages is predominantly due to the caffeine. 

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. 

The three methalated xanthine derivatives (methyixanthines) theophylline, theobromine, and caffeine are plant alkaloids. Theophylline is the only one of these which is widely used therapeutically. Three possible modes of action have been proposed ... 

Many genera and species contain caffeine and other xanthines. Pyrrolidoncs, pyridones, and polypeptide alkaloids are also found in the family. 

The purine nucleus is constructed by a condensation of the pyrimidine and imidazole (glyoxaline) nuclei (Figure 11.12). Xanthine is 2,6-dioxypurine caffeine, 1,3,7-trimethylxanthine theophylline, 1,3-dimethylxanthine and theobromine, 3,7-dimethylxanthine. These alkaloids are found in coffee, tea, cacao, kola, mate, and guarana (Figure 11.13). 

The prototypical structural class of nonselective PDE inhibitors is represented by the methylxanthines (Figure 9.4), a family of plant-derived alkaloids that includes theophylline (1), caffeine (2), and theobromine (3) [9], Although limited in potency, these simple naturally occurring xanthines were the parents in the later discoveries of more potent synthetic derivatives such as pentoxyfylline (4) and isobutylmethyl-xanthine (IBMX, 5). In particular, the latter compound has been widely used and has been regarded for decades as the gold standard nonselective inhibitor of all PDEs. Only recently has it become clear that some of the newer PDEs (8 and 9) are not inhibited by IBMX. Derivatives of IBMX carrying substituents at the 8 position confer increased potency [10], An example is compound 6, which retains most of... 

The two alkaloids theobromine and theophylline are isomeric, theobromine being the 3-7-di-methyl xanthine and theophylline the I-3-di-methyl xanthine. Theobromine is the principal alkaloid of the cocoa bean. Cacao theohroma. It occurs also in small amounts in kola nuts and tea leaves. Theophylline is present in small amounts in tea. They both resemble caffeine in being crystalline, weak bases. 

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