Caffeine synthesis

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). 

Beryllium, calcium, boron, and aluminum act in a similar manner. Malonic acid is made from monochloroacetic acid by reaction with potassium cyanide followed by hydrolysis. The acid and the intermediate cyanoacetic acid are used for the synthesis of polymethine dyes, synthetic caffeine, and for the manufacture of diethyl malonate, which is used in the synthesis of barbiturates. Most metals dissolve in aqueous potassium cyanide solutions in the presence of oxygen to form complex cyanides (see Coordination compounds). 

Seasonal variations in the metabolic fate of adenine nucleotides prelabelled with [8—1-4C] adenine were examined in leaf disks prepared at 1-month intervals, over the course of 1 year, from the shoots of tea plants (Camellia sinensis L. cv. Yabukita) which were growing under natural field conditions by Fujimori et al.33 Incorporation of radioactivity into nucleic acids and catabolites of purine nucleotides was found throughout the experimental period, but incorporation into theobromine and caffeine was found only in the young leaves harvested from April to June. Methy-lation of xanthosine, 7-methylxanthine, and theobromine was catalyzed by gel-filtered leaf extracts from young shoots (April to June), but the reactions could not be detected in extracts from leaves in which no synthesis of caffeine was observed in vivo. By contrast, the activity of 5-phosphoribosyl-1-pyrophosphate synthetase was still found in leaves harvested in July and August. 

Mazzafera, P, Wingsle, G., Olsson, O., Sandberg, G., S-adensoyl-L-methionine theobromine 1-N-methyltranferase, a enzyme catalyzing the synthesis of caffeine in coffee Phytochemistry 37 1577 1994... 

Fujimori, N., Suzuki, T., and Ashihara, H., Seasonal variations in biosynthetic capacity for the synthesis of caffeine in tea leave, Phytochemistry, 30,2245,1991... 

The various chemical processes influencing the colour formation in tea have been vigorously investigated. The self-association of black tea polyphenol theaflavin and its com-plexation with caffeine [175], and the role of epicatechin quinone in the synthesis and degradation of theaflavin [176] have been studied in detail. 

Uses A mixture of cis and trans isomers is used as a solvent for fats, phenols, camphor ingredient in perfumes low temperature solvent for sensitive substances such as caffeine refrigerant organic synthesis. 

Stimulants. From coca leaves chewed by native laborers in South America to brewed teas and coffees used across the globe, stimulants have been used since antiquity. In these essentially naturally occurring forms, coca and caffeine were long known to provide a boost of energy, focus attention, and decrease appetite. However, compared to today s refined stimulants, the effects were relatively mild. There is no clear evidence that these substances were used to treat the ancient antecedents of psychiatric illness in past cultures. The isolation of cocaine in the mid-1700s and the synthesis of amphetamine in the late 1800s dramatically increased stimulant use (and abuse) in society. 

Caffeine and theobromine may be obtained in large quantities from natural sources, or they may be obtained by total or partial synthesis. Theophylline is usually produced by total synthesis. 

I which was 20 times stronger than that of caffeine. By the systematic synthesis of bitter... 

The first step in the Fourier synthesis of the caffeine-pyrogallol complex was to choose an initial model so an electron density projection could be calculated. From the previous results it was determined that the unit cell was tetragonal measuring 23.26 X 23.26 X 6.99 A., and that eight caffeine-pyrogallol complex moieties reside in the unit cell. This information alone does not give any indication of the way in which the molecules are packed inside the unit cell, but the symmetry operations of the space group can be used to eliminate many models. For example, one of the symmetry operators in the unit cell is a fourfold axis. 

As indicated in Fig. 25-18, free adenine released from catabolism of nucleic acids can be deaminated hydrolytically to hypoxanthine, and guanine can be deaminated to xanthine.328 The molybdenum-containing xanthine oxidase (Chapter 16) oxidizes hypoxanthine to xanthine and the latter on to uric acid. Some Clostridia convert purine or hypoxanthine to xanthine by the action of a selenium-containing purine hydroxylase.3283 Another reaction of xanthine occurring in some plants is conversion to the trimethylated derivative caffeine. 328b One of the physiological effects of caffeine in animals is inhibition of pyrimidine synthesis.329 However, the effect most sought by coffee drinkers may be an increase in blood pressure caused by occupancy of adenosine receptors by caffeine.330... 

---