7- theophylline 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). 

Theophylline, 7-alkoxy-8-methyl-reactions, 5, 554 Theophylline, 8-alkyl-synthesis, 5, 573 Theophylline, 8-aryl-... 

Theophylline, 9-aryl-synthesis, 5, 576 Theophylline, 8-arylamino-synthesis, 5, 576 Theophylline, 9-benzyl-rearrangement, 5, 534 Theophylline, 8-chloro-reduction, 5, 541 Theophylline, 6-deoxy-reduction, 5, 541 Theophylline, 8-dimethylamino-synthesis, 5, 580 Theophylline, 8-methyl-synthesis, 5, 591 Theophylline, 8-methylthio-synthesis, 5, 578 Theophylline, 8-nitro-synthesis, 5, 538 Theophylline, 7-phenyl-synthesis, 5, 581 Theophylline, 8-phenyl-7-oxide... 

This paper concerns the synthesis and characterization of amphiphilic networks comprising PHEMA and PIB segments. Sustained release studies with theophylline-loaded networks are also described. 

In 1973, the synthesis of amino acids containing pendant theophylline and other nucleic acid bases, and the polymerization of NCA compounds derived therefrom have studied by our group ( 16). 

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. 

N-Aminooxazolidone, 228 6-Aminopenicillanic acid (6-APA), 409, 410 Aminophenazole, 248 p-Aminophenol, 111 Aminophylline, see theophylline Amlnopromazine, 390 Aminopropylon, 234 2-Aminopyrimidine synthesis, 127, 128... 

Tetrydamine, 352 Thalidomide, 296 Thebaine, 318 Theniurn closylate, 99 Theobromine, 456 Theophylline, 464 Thiabendazole, 352, 353 1,2,5-Thiadiazole synthesis,... 

Theophilline is also a minor constituent of tea, but is prepared by direct chemical synthesis for medical use. It functions to relax smooth muscle and, therefore, can be used as a bronchodilator in the treatment of asthma and bronchitis. Aminophylline is a derivative of theophilline (theophylline ethylenediamine), which is often used in place of theophilline due to its greater aqueous solubility. 

Bronchodilation is promoted by cAMP. Intracellular levels of cAMP can be increased by 13-adrenoceptor agonists, which increase the rate of its synthesis by adenylyl cyclase (AC) or by phosphodiesterase (PDE) inhibitors such as theophylline, which slow the rate of its degradation. Bronchoconstriction can be inhibited by muscarinic antagonists and possibly by adenosine antagonists. 

The synthesis of 7-(2,3,6-trideoxy-/ -L-gh/cero-hex-2-enopyranosyl-4-ulose)theophylline (71), which constitutes an important intermediate in the synthesis of branched-chain nucleosides (see Section VI), has been achieved42 by reaction54 55 of the 2, 3 -anhydroketonucleoside 59 with sodium iodide and sodium acetate. 

Among the unsaturated ketonucleosides may be classified the disaccharide derivative 74, which is an analog of the biologically active compound 68c. The key intermediate for the synthesis of this unsaturated ketodisaccharide nucleoside was the partially protected, disaccharide nucleoside 73, which was prepared by two separate routes,56 Treatment of 73 with the Me2SO-acetic anhydride reagent for two days at room temperature afforded 7-[2,3-di-0-benzoyl-4-0-(3-0-benzoyl-2,6-di-deoxy - / - d - glycero - hex - 2 - enopyranosyl - 4 - ulose) - 6 - deoxy - / - d -glycopyranosyl]theophylline (74), isolated crystalline.56... 

Caffeine is used medicinally as a CNS stimulant, usually combined with another therapeutic agent, as in compound analgesic preparations. Theobromine is of value as a diuretic and smooth muscle relaxant, but is not now routinely used. Theophylline is an important smooth muscle relaxant for relief of bronchospasm, and is frequently dispensed in slow-release formulations to reduce side-effects. It is also available as aminophylline (a more soluble preparation containing theophylline with ethylenediamine) and choline theophyllinate (theophylline and choline). The alkaloids may be isolated from natural sources, or obtained by total or partial synthesis. 

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