Theophylline 7- -, acetylation with acetic

The course of acid-catalyzed acetylations with acetic anhydride may depend markedly on the concentration of the acid and the type of acid. Reaction of 7-(3-deoxy-3-nitro-/3-D-galactopyrano-syl)theophylline with acetic anhydride in the presence of one molar equivalent of perchloric acid gave the 2, 4, 6 -triacetate in 89% yield, but, in the presence of only a trace of the acid, 82% of the 4, 6 -diacetate was obtained.93 Treatment of the manno isomer of the nucleoside with acetic anhydride-boron trifluoride gave the 4, 6 -diacetate as a crystalline product (24%), whereas phosphoric acid as the catalyst yielded the 2, 4, 6 -triester (45%). 

Some examples of the behavior of unsaturated ketonucleosides under alkaline conditions have also been reported. The enol acetate 61a is more stable than the parent ketonucleoside 36a. In 0.1 M methanolic sodium hydroxide, free theophylline was detected only after 4 h, by which time, loss of the acetyl group was complete a reaction time of more than 18 h was needed for complete cleavage of the glycosylic bond.51 In alcoholic solution, the unsaturated 4 -ketonucleoside 66 was very sensitive to nucleophilic attack, and decomposed rapidly, with elimination of the nitrogenous base.31 Thus, treatment with sodium borohydride at — 70° led to complete decomposition within 10 min but, when sodium borohydride was added to a solution of 66 in 1,2-dichloroethane containing acetic acid, fast reduction occurred, and no degradation was observed.31... 

Fast reduction was observed when the unsaturated 4 -ketonucleoside 66 was treated with sodium borohydride in solution in 1,2-dichloroeth-ane containing acetic acid.31 An unexpected attack from the most-hindered side gave 7-(4,6-di-0-acetyl-2-deoxy-/ -D-arahino-hexopyrano-syl)theophylline (92) almost exclusively. The mechanism proposed... 

Addition of ammonia to 71 was less stereospecific than the addition50 of amine to bromoketonucleoside 72b. Thus, treatment of 71 with ammonia in acetonitrile, and acetylation of the product, gave a mixture of erythro and threo acetamido-nucleosides from which only the 7-(2-acet-amido - 2,3,6 - trideoxy -/ - l - threo - hexopyranosyl - 4 - ulose)theophylline (104) could be isolated.42... 

S3mthesis of Xanthine.— The synthesis of xanthine which is the immediate mother substance of theobromine, theophylline and caffeine has been accomplished as follows Starting with urea or carbamide, this is treated with cyano acetic acid in the presence of phosphorus oxychloride whereby the cyan acetyl radical is introduced into urea. The cyan acetyl urea by treatment with sodium hydroxide yields an isomeric imino compound. 

A comparison between three standard methods of synthesis of purine nucleosides, namely fusion, condensation of acetylated glycosyl chlorides, and from 1-acetates in the presence of titanium(iv) chloride has been made. Thus when the glucosaminyl acetate (1) was fused with theophylline in the presence of p-toluenesulphonic acid and p-nitrophenol, a 45 % yield of the nucleoside (2) was obtained. In contrast to the findings of Ishido et al. Carbohydrate Res., 1975, 44, 215), lower yields were obtained when the activating agents were omitted. The nucleoside (3) synthesized in 32 % yield from the glucosyl acetate... 

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