1.3.7- Trimethylxanthine, caffeine

Tea leaf contains 2.5-4.0% caffeine (1,3,7-trimethylxanthine) on a dry weight basis and smaller quantities of the related methylxanthines, theobromine (3,7-dimethylxanthine 0.2-0.4%) and theophylline (1,3-dimethylxanthine ca. 0.02%). Although it is said that var. sinensis is slightly lower in caffeine than var. assamica, black, green and oolong tea beverages all contain about the same levels of caffeine (Cheng and Chen, 1994). 

The methylxanthines of interest are caffeine (1,3,7-trimethylxanthine), theophylline (1,3-dimethylxanthine), and theobromine (3,7-dimethylxanthine) and they occur in coffee, tea, mate, cocoa products, and cola beverages. This chapter is an introduction to their chemistry, isolation, and biosynthesis. While the class of methylxanthines is large and comprised of more members than these three, this chapter will essentially be limited to caffeine, theobromine, and theophylline. 

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, 1,3,7-trimethylxanthine, is the major alkaloid, occms in teaplants, coffee, guarana, cola nuts, cocoa beans, mate and other plants. It is a powerful stimirlant of the central nervous system and also stimirlates the cardiac muscle. However, high... 

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). 

Antioxidant activities of caffeine (1,3,7-trimethylxanthine) and its main metabolites was compared. Caffeine, 1,7-dimethylxanthine, and 3,7-dimethylxanthine did not show any peroxyl radical-scavenging capacity at concentration up to 100 fxM. Flowever, the relative antioxidant activities (with respect to Trolox) of 1-methyl-xanthine and 1-methyluric acid were 0.82 and 0.58, respectively (L9). 

Caffeine (1,3,7-trimethylxanthine) Theophylline (1,3-dimethylxanthine) Theobromine (3,7-dimethylxanthine)... 

Caffeine (= 1,3,7-Trimethylxanthine Coffeine Guaranine Thein Theine) (purine, methylxanthine) the plant bioactive most consumed by humans ... 

Caffeine (= 1,3,7-Trimethylxanthine Coffeine Guaranine Thein Theine)... 

Almost identical bell-shaped rate-pH curves are produced by [8- H]theophylline (1,3-dimethylxanthine 8), xanthine (77T803) and 1-methylxanthine (79T663) whereas the characteristic curve shown by 9-isopropylpurine is also reproduced by [8- H]caffeine (1,3,7-trimethylxanthine) (77T803), [8- H]-theobromine (3,7-dimethylxanthine), 7-methylxanthine and xanthosine (79T663) in which substituents also occur in the imidazole ring. 3-Methylxanthine (71) on the other hand shows a rate-pH profile which is exceptional. 

In most studies, the selectivities of the MIPs have been estimated by measuring the amount of each ligand required to displace 50% of the binding of radiolabelled imprint species to the MIP (IC50). The first MIA study reported excellent selectivity of the theophylline method for theophylline (1,3-dimethylxanthine) in the presence of the structurally related compound caffeine (1,3,7-trimethylxanthine) [3]. Despite their close resemblance (they differ by only one methyl group), caffeine showed less than 1 % cross-reactivity. A similar level of specificity was recorded for cortisol and corticosterone MIPs, which were able to detect the absence and presence of single hydroxyl groups and double bonds in the steroid structure [13]. 

Caffeine", 1,3,7-trimethylxanthine, has been discussed previously and is used as a CNS, respiratory, and cardiac stimulant. 

Caffeine (1,3,7-trimethylxanthine) is the well known stimulant present in tea and coffee. In mammals the end product of metabolic breakdown of nucleic acids is urea, but in birds and reptiles it is uric acid uric acid was one of the first heterocyclic compounds to be isolated as a pure substance, for it was obtained from gallstones by Scheele in 1776. 

Methylxanthines and methyluric acids are secondary plant metabolites derived from purine nucleotides (Figure 6.59). The most well-known methylxanthines are caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine), which occur in tea (Camellia sinensis. Camellia ptilophylla, and Camellia taliensis) [242,243], coffee (Coffea arabica, Coffea canephora) [244, 245], cacao (Theobroma cacao) [246], and a number of other nonalcoholic beverages of plant origin Ilex paraguariensis, Paullinia cupana. Cola species and Citrus species [247-249]... 

As commented above, the use of a surfactant different from SDS is anecdotal in direct injection MLC procedures. For this reason, the comparison of the determination of a drug such as theophylline (1,3 -dimethylxanthine), using two different surfactants, is interesting. Habel et al. [9] reported a procedure for the direct determination of this drug in human serum by using a p-Bondapak phenyl column, a micellar mobile phase of the zwitterionic surfactant C DAPS (10 M) containing 3% 1-propanol and UV detection at 273 nm. Later, Perez Martinez et al. [29] developed a procedure for theophylline, caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine), in urine, with a Spherisorb Cl8... 

The most well-known purine alkaloid is caffeine (1,3,7-trimethylxanthine) 1 which, along with theobromine (3,7-dimethylxanthine) 2, accumulates in leaves of tea and mate and beans of coffee and cacao, which are popular components of nonalcoholic beverages and/or chocolate products [2]. The pharmacological effects of purine alkaloids in animals, such as stimulation of the central nervous system, have been investigated extensively [3]. Caffeine is also often utilized in cytological studies to induce the formation of binucleate cells and is, therefore, used to measure the duration of the mitotic cycle [4]. 

The best known N-compound is caffeine (1,3,7-trimethylxanthine) because of its physiological effects (stimulation of the central nervous system, increased blood circulation and respiration). It is mildly bitter in taste (threshold value in water is 0.8-1.2 mmole/1), crystallizes with one molecule of water into silky, white needles, which melt at 236.5 °C and subhme without decomposition at 178 °C. The caffeine content of raw Arabica coffee is 0.9-1.4%, while in the Robusta variety, it is 1.5-2.6%. In contrast there are caffeine-free Coffea varieties. Santos, an Arabica coffee, is on the low side, while Robusta from Angola is at the top of the range given for caffeine content. Other purine alkaloids are theobromine (Arabica 36-40 mg/kg, Robusta 26-82 mg/kg)... 

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... 

Methylated xanthines have pharmacologic applications (theophylline = 1,3-di-methylxanthine, caffeine = 1,3,7-trimethylxanthine). Certain analogs of the purines (8-azaguanine, 6-mercaptopurine) have antibiotic and cytostatic properties they have been used as chemotherapeutic agents against tumors. 

The xanthine family give rise to a number of natural products such as caffeine (1,3,7-trimethylxanthine). Caffeine pharmacology involves adenosine receptor antagonism but details remain elusive. The xanthine backbone forms the basis of a large number of derivatives acting as adenosine receptor antagonists. 

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