Tetra-O-acetyl-D-ribofuranose

N-3 (78JMC112). Treatment of 7-chloro-l-(tri-0-acetyl-/3-D-ribofuranosyl)imidazo[4,5-f>]pyridine with tetra-O-acetyl-D-ribofuranose and HgBr2 produced the 3-isomer in 75.9% yield with the indication that transglycosylation proceeds through the l,3-bis(glycosyl) intermediate to the thermodynamically more stable 3-isomer (82Mi4iooi), confirming the relative stabilites mentioned above. 

Illustrative of the fusion method, 6-methylthio-8-azapurine and 1-0-ace-tyl-2,3,5-tri-0-benzoyl-a-D-arabinofuranose, when fused at 200 C, gave the 7-, 8-, and 9-arabinosides in 5,24, and 37% yields, respectively. A similar reaction to make the ribofuranoside benefited from the catalytic action of bis-p-nitrophenyl phosphate. In an attempt to obtain the anomer, 6-methylthio-8-azapurine and 2,3,5-tri-O-benzyl- D-arabinofuranosyl chloride were fused (120 C, 45 min). Even under these mUder conditions, much anomerization to the unwanted a isomer occurred. In a modificaction of the fusion reaction, tetra-O-acetyl-D-ribofuranose was heated with 6-nonan-oylamino-8-azapurine to give azaadenosine in 14% yield. ... 

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. 

Nebularine has long been known as a metabolite of Clitocybe nebularis (383), revealing tuberculostatic and antimitotic activity (383-385). Few syntheses of this compound having a 9-(D-ribosyl)purine structure have been reported, namely, the Brown (386) approach, starting from a chloro-mercuri-6-purine and 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride, the Fox (387) procedure, based on the transformation of inosine to nebularine via a desulfurization by Raney nickel of the thioinosine intermediate, and the Iwamura-Hashizume (384,388) method, in which nebularine and its N-7 isomer were synthesized simultaneously by the fusion of purine and tetra-O-acetyl-D-ribofuranose using bis(p-nitrophenyl)hydrogen phosphate as the catalyst. 

CH3COO OCOCH3 A mixture of N -octanoyladenine, 1,2,3,5-tetra-O-acetyl- -D-ribofuranose, and AICI3 refluxed 2 hrs. in chlorobenzene, the crude intermediate dissolved in metha-... 

Cl3H1eOg, 1,2,3,4-Tetra-O-acetyl-a-D-ribopyranose, 43B, 547 Cl3H1gOs, 1,2,3,4-Tetra-O-acetyl- -D-arabinopyranose, 4OB, 398 Cl3H1gOs, 1,2,3,4-Tetra-O-acetyl- -D-xylopyranose, 42B, 324 CigHigOg, 1,2,3,5-Tetra-O-acetyl- -D-ribofuranose, 39B, 313 42B,... 

Protection of Carbohydrates. Protected carbohydrates (4 and 5), having one free hydroxyl and a phenylseleno group on the adjacent carbon, were obtained by treatment of commercially available tetra-O-acetyl- -D-ribofuranose with PhSeH/BFs Et20, followed by hydrolysis and silylation with TIPDSCI2 in pyridine (reported yields are 77-80%). As expected, the silyl chloride reacts much faster with primary than secondary alcohols, regiospecifically affording the desired protection. 

Almost thirty years passed before Todd and coworkers applied the Fischer-Helferich procedure to the synthesis of the natural purine nucleosides, adenosine (l)i and guanosine (2). Condensation of tri-O-acetyl-D-ribofuranosyl chloride, prepared from 5-0-benzyl-D-ribose by way of tetra-0-acetyl-D-ribofuranose,i 2 with the silver salt of 2,8-dichloroadenine... 

Tetra-0-acetyl-p-D-ribofuranose, R-138 Tetra-O-acetyl-D-ribonic acid, R-128... 

The synthesis of corresponding pyrimidine nucleosides was not possible by the mercuric chloride method. The syntheses succeeded, however, on application of the Hilbert—Johnson procedure. Tetra-O-acetyl-4-thio-D-ribofuranose was transformed with ethereal hydrogen chloride into the glycosyl chloride derivative 254, and this was directly heated for five days with 2,4-diethoxy-5-methylpyrimidine. The anomeric forms of 4-ethoxy-5-methyl-l-(2,3,5-tri-0-acetyl-4-thio-D-ribofuranosyl)-2(lH)-pyrimidinone obtained could be separated... 

Ribosidation of the trimethylsilyl derivative of 2-hydroxypyrazine (69) (prepared with trimethylsilyl chloride and bistrimethylsilylamine) with 1,2,3,5-tetra-O-acetyl-/J-D-ribofuranose and titanium tetrachloride in 1,2-dichloroethane, followed by deacetylation with sodium methoxide, gave 2-oxo-l-( -D-ribofuranosyl)-l, 2-dihydropyrazine and its 4-oxide was prepared similarly (1035). A similar reaction occurred with the trimethylsilyl derivative of 3-hydroxypyrazine 1-oxide and 1,2,3-tri-<3-acetyl-D-erythrose (1110). 

The synthesis of IV-ribofuranosyltriazoles, for use as metabolite analogs of the purine-forming imidazoles, provides a different aspect of N-alkylation in the triazole series. Acid-catalyzed fusion of 4-nitrotriazole with tetra-O-acetyl-/3-D-ribofuranose gave 2-/5-D-ribofuranosyl-4-nitrotriazole (175°C, 45 min, 58%), accompanied by 24% yield of the 1-ribofuranosyl isomer. The acetyl groups were removed with cold methanolic sodium methoxide (85% yield), and the nitro group reduced to a primary amine with hydrazine hydrate over palladium in methanol (25°C, 93%) (72JHC1195). 

Aminotriazole, and some of its 5-substituted derivatives, when fused with 1,2,3,5-tetra-O-acetyl- or -benzoyl-/ -D-ribofuranose, gave a 1 1-mixture of 2- and 3-ribofuranosyltriazoles (76USP3968103). 4-Acetamidotriazole-5-carboxamide, mercuric cyanide, and tri-0-benzoyl-/ -D-ribofuranosyl chloride, when refluxed in nitromethane, furnished 4-acetamido-l- 2, 3, 5-tri-O-benzoyl-/S-D-ribofuranosyl)triazole-5-carboxamide (3 hr, 48%), from which the benzoyl groups were removed in methanolic ammonia (0°C, 3 days, 54%) (72BCJ2577). Occupation of the 1 position in this and other ribosylations was unexpected but was carefully verified. 

Conversion of tetra-0-acetyl-/3-D-ribopyranose into methyl 1-thio-/3-D-ribopyranoside, by the action of methanethiol and zinc chloride, with subsequent deacetylation, is accompanied by the formation of substantial proportions of methyl l,5-dithio-j8-D-ribopyranoside (55) and 4-S-methyl-4-thio-L-lyxose dimethyl dithioacetal (53), plus a trace of 5-S-methyl-5-thio-D-ribose dimethyl dithioacetal (56). Although similar treatment of tetra-O-acetyl-jS-D-ribofuranose for a short time produced the expected methyl 1-thio-jS-D-... 

Glycosylation of 7-nitro-IbP 277 with 1,2,3,5-tetra-O-acetyl-jS-D-ribofuranose (TAR) and SnCU gave a mixture of N-3 and N-4 jS-isomers 278 and 279 in 87% overall yield. The sodium salt of the same 7-nitro-IbP 277 at 25 °C with l-chloro-2-deoxy-3,5-di(p-toluyl)-D-erythro-pentafuranose in MeCN was converted into a single N-3 jS-isomer 280 in a good yield (95TL1601). 

Heating at reflux IbP-4-oxide 281 in a mixture of hexamethyldisilazane and pyridine (1 1 ratio) for 4h in the presence of a catalytic quantity of (NH4)2S04 provided trimethylsilyl derivative 282 of the parent. Stirring this product with 1,2,3,5-tetra-O-acetyl- S-D-ribofuranose and SnCU at room temperature for 18 h resulted in a high yield of substituted 3-ribosyl-l/f-IbP 4-oxide (283) (82JHC513). 

High yields of 2,3,5 -tri-O-acetyl- and -O-benzoyl-adenosine have been obtained from the corresponding 1-0-acetyl- -D-ribofuranose derivative by direct reaction with unprotected adenine in acetonitrile in presence of stannic chloride. Ribosylation of the silylated imidazolethione (7) with the glycosyl chloride (8) in presence of stannic chloride or silver perchlorate gave mainly the diribosyl derivative (9) rather than the expected mono-ribosyl nucleoside (10) (2 1 ratio), whereas use of the tetra-acetyl sugar (11) gave mainly (10). ... 

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