Caffeine nucleosides

In aqueous solution, caffeine associates to form at least a dimer and probably a polymer 12 the molecules are arranged in a stack.13 Caffeine will also associate with purines and pyrimidines either as the free bases or as their nucleosides.13 Caffeine crystallizes from water as a monohydrate [9],... 

Roberts, M. F., Waller, G. R., N methyltransferases and 7-methyl-N-nucleoside hydrolase activity in Coffea arabica and the biosynthesis of caffeine, Phytochemistry, 18, 451, 1979. (CA92 18866w)... 

Purine derivatives with neurotransmitter function are all derived from adenine-containing nucleotides or nucleosides. ATP is released along with acetylcholine and other transmitters, and among other functions it regulates the emission of transmitters from its synapse of origin. The stimulatory effect of caffeine is mainly based on the fact that it binds to adenosine receptors. 

Many antibiotics produced by various microorganisms are nucleosides (2). Among these are nebularine, cordycepin, and nucleocidin. The only known purines in higher plants shown to be involved In allelopathy are caffeine, theophylline, paraxanthine, and theobromine from the coffee tree... 

Adenosine is a nucleoside that occurs naturally throughout the body. Its half-life in the blood is less than 10 seconds. Its mechanism of action involves activation of an inward rectifier K+ current and inhibition of calcium current. The results of these actions are marked hyperpolarization and suppression of calcium-dependent action potentials. When given as a bolus dose, adenosine directly inhibits atrioventricular nodal conduction and increases the atrioventricular nodal refractory period but has lesser effects on the sinoatrial node. Adenosine is currently the drug of choice for prompt conversion of paroxysmal supraventricular tachycardia to sinus rhythm because of its high efficacy (90-95%) and very short duration of action. It is usually given in a bolus dose of 6 mg followed, if necessary, by a dose of 12 mg. An uncommon variant of ventricular tachycardia is adenosine-sensitive. The drug is less effective in the presence of adenosine receptor blockers such as theophylline or caffeine, and its effects are potentiated by adenosine uptake inhibitors such as dipyridamole. 

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... 

Caffeine is one more example of compounds belonging to the purines. Evenari (21) has reported that it is one of the potent inhibitors of seed germination. Several substituted purines and nucleosides produced by microorganisms are effective antibiotics (see the Section 11). They include nebularine, cordycepin and nucleocidine which may also possess growth-inhibiting properties, as is the case with other antibiotics (Figure 10). 

The direct introduction of chlorine into the 8-position of purine nucleosides is more difficult than bromination. The course of chlorination is considerably affected by the nature of the solvent used. Thus, theobromine is converted to 8-chlorothcobromine by action of chlorine in chloroform. Theophylline, caffeine and sulfanyl analogs of these purines are chlorinated in a similar manner. ... 

Plates, leaflets from acetore-alc, faint greenish-yellow tinge, tnp 122-123. Maximum fluorescence at 440 nm C.A. 38, 1276 (1944), Freely sol in benzene moderately sol in acetone slightly so] in alcohol. Insol in water. May be solubilized in water by purines such as caffeine, tetramethyl-uric acid- The nucleosides, adeDOStne, and guanosine also show a solvent action. 

Occurrence In small amounts in muscles, liver, urinary calculi, beet juice, barley shoots, fly agarics, peanut kernels, potatoes, yeasts, coffee beans, tea leaves. X. is formed in the metabolism of higher animals by deamination of guanine (component of nucleic acid) or oxidation of hypoxanthine by xanthine oxidase present in muscles which then also oxidizes X. further to uric acid, the final product of the purine metabolism in humans. The nucleoside derived from X. is xanthosine. Although X. is chemically closely related to "caffein(e) and other methylxanthines, its activity is different. Stimulation of the central nervous system is less pronounced, the paralyzing effects dominate, and cardiac muscles are severely damaged. 

In the case of DNA, a D-2-deoxyribose molecule is combined to each of the bases to form a nucleoside, and the nucleosides are then combined with each other with a phosphoric acid to form a polymer (DNA). On the other hand, in the case of RNA, D-ribose, instead of D-2-deoxyribose, is combined to each of the bases to form a nucleoside, and as in the case of DNA, these nucleosides are combined with each other to form a polymer (RNA). Among the bases within DNA and RNA, adenine and guanine have been described in the preceding section. In this section, cytosine, thymine, and uracil, which are pyrimidine bases, will be described. Purine derivatives exist as a constituent unit of nucleic acids and as many kinds of monomers, and these are also present in natural products, such as caffeine, inosinic acid, and cytokinin. On the other hand, as natural products, pyrimidine derivatives are rather rare. Nucleosides composed of pyrimidine bases cytosine, thymine, and uracil coupled with D-ribose are known as cytidine, thymidine, and uridine, respectively. Among these alkaloids, cytidine was first isolated from the nucleic acid of yeast [1,2], and thymidine was isolated from thymonucleic acid [3,4]. In the meantime, uridine was obtained by the weak alkali hydrolysis [5] of the nucleic acids originating from yeast. 

Camellia (Thea) sinensis (tea) and Cqffea arabica (coffee) plants. Caffeine was formed rapidly by extracts of green coffee berries, but little by more mature ones, and not at all by seedlings. Biosynthesis of caffein proceeds from 7-methylxanthosine in the presence of an active purine nucleoside phosphorylase or 7-methyl-A -nucleoside hydrolase. Methionine and 5-adenosylmethionine serve as precursors for the methyl groups of purine alkaloids. These act in the presence of methyltransferases on 7-methylxanthine (38) and theobromine (31) to produce caffeine. A pathway for the origin of these compounds in coffee and tea plants has been proposed (Suzuki et al., 1992 Waller and Dermer, 1981) (Fig. 37.10). 

The A1 receptor apparently mediates an inhibitory effect of adenosine, N°-L-phenylisopropyl-adenosine (L-PIA) and 2-Chloroadenosine on adenylate cyclase (19). Low concentrations of these nucleosides also block the cAMP accumulation induced by agonists of adenylate cyclase, such as isoproterenol and PGE2 (21). Adenosine and its derivatives have an high affinity for this site and their effects are also blocked by xanthines such as caffeine and theophylline (22). 

The purine bases, caffeine, theophylline, and theobromine, yield the corresponding 6-monothio- and 2,6-dithio derivatives upon reaction with LR without a solvent under microwave irradiation. Thionation of the carbonyl groups in the nucleobases of nucleotides leads to interesting special types of thiolactams, which are expected to exhibit modified biological activities. P3u imidine nucleosides are selectively thionated in the 4-position of the nu-cleobase. The mild reaction conditions applied allow the conversion of nucleosides with labile glycosidic bonds, such as 5,6-dihydropyrimidine-(113) and 2, 3 -dideoxynucleosides. Thiononucleosides with unnatural bases (114) or sugar moieties (115), (116) can also be prepared. 

Few purine bases and nucleosides have been isolated from Octocorallia, but recall the historical significance of the discovery of arabinosyladenine (Ara-A) in the gorgo-nian Eunicella cavolini (see Chapter 4) and the identification of caffeine in the two gorgonians Paramuricea chamaleon (Imre et al., 1987) and Villagorgia rubra (Espada et al., 1993). 

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