Nucleoside fusion synthesis

N-Glycosyl-N-hetepocyclics from acyl glycosides Nucleoside fusion synthesis... 

Nucleoside 5 -phosphates are employed as starting materials to prepare the activated derivatives (56). Their synthesis has been discussed in a Chapter in this Series.266 The methods used most frequently for preparing glycosyl phosphates involve the interaction of protected glycosyl bromides with diphenyl phosphate and subsequent removal of the protective groups,267 or by fusion of the peracetylated monosaccharides with anhydrous phosphoric acid.268... 

An interesting approach149 to the synthesis of partially protected nucleosides involved fusion for 12 hours at 130° of 5 -0-acetyladenosine and 2, 3, 5 -tri-0-acetyladenosine, followed by separation, by countercurrent distribution, of the so-formed mixture of 3, 5 -di-0-acetyl-, 5 -0-acetyl-, and 2, 3, 5 -tri-0-acetyladenosine. It is noteworthy that no 2, 5 -diester was isolated. A variation154 of this procedure was the fusion, at —200°, of a mixture of 2, 3, 5 -tri-0-acetyladenosine and adenosine, which yielded the 2, 3, 5 -triacetate, the 2, 3 -diacetate, and the 3, 5 -diacetate, with the last preponderating. 

The alternative fusion method for nucleoside synthesis involves the reaction of a purine with an acylated sugar in the presence of a suitable acid such as p-toluenesulfonic acid or a compound such as tin(IV) chloride or antimony chloride. One of many examples includes the preparation (48% yield) of 2,6-dibromo-9-(j8-D-ribofuranosyl)purine by fusion at 130 °C over 30 minutes of l,2,3,5-tetra-0-acetyl-j8-D-ribose with 2,6-dibromopurine in the presence of p-toluenesulfonic acid (B-68Mi4090i, p. 180). 

The prototype of the fusion method for the synthesis of a nucleoside is the condensation of 2,6-dichloropurine with 1,2,3,5-tetra-O-acetylribofuranose at 130°C to give 10. The reaction proceeds in good yield, with or without catalyst. It seems that the more acidic heterocydes, such as purines with electron-withdrawing groups, undergo the fusion reaction autocatalytically. 

The preparation of nucleosides by the fusion method continues to be employed extensively. Iodine has been found to be a good catalyst for the synthesis of certain nucleosides by the fusion method. Nebularine has been synthesized in high yield by the fusion technique using bis- (p-nitrophenyl)hydrogen phosphate as the catalyst. The synthesis of 2 -C-methyladenosine has been accomplished from the protected 2-C-methyl-D-ribono-7-lactone (I) which was reduced with bis- (3-methvl-2-butyl)borane-(disiamylborane). The corresponding tetrabenzoyl derivative was converted... 

Nucleoside synthesis.3 This reagent is superior to p-toluenesulfonic acid, ethyl polyphosphate, or zinc chloride for the preparation of nucleosides by fusion of purines with fully acetylated pentoses or hexoses. An example of the method4 is the fusion of purine (1) with tetra-O-acetyl-D-ribofuranose (2) at 174-180° (at the water pump vacuum) to give the two nucleosides (3) and (4). The main product (3) is the triacetyl derivative of a naturally occurring nucleoside antibiotic nebularine. 

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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