Ribofuranose preparation

Of the four possible 5-deoxy-pent-4-enofuranoses, the D-erythro-isomer was of interest as a potential source of derivatives of L-lyxofuranose. For this purpose, a vinyl ether having the D-en/ hro-configuration has been prepared from derivatives of D-ribose. Condensation of D-ribose with acetone in the presence of methanol, cupric sulfate and sulfuric acid at 30°C., as described by Levene and Stiller(30) afforded a sirupy product consisting mainly of methyl 2,3-O-isopropylidene-D-ribofuranose (40). Treatment of a pyridine solution of the sirup with tosyl chloride... 

The preparation of glycosyl fluorides is described next. Aiming to have a convenient glycosyl donor convertible into 1,2-CM-furanosides, Mukaiyama and coworkers prepared 2,3,5-tri-O-benzyl-yS-D-ribofuranosyl fluoride (36y3) by treatment of a protected D-ribofuranose (35) with 2-fluoro-1 -meth-ylpyridinium tosylate (FMPTs) the total yield was raised by anomerizing the simultaneously produced a-1-fluoride (36a, 7, p 66, 72.f 24 Hz) to 36 (7, F 63.5 Hz, 72,F very small ) by treatment with BF3-OEt2. 

Preparation of 2-fluorofuranoses is also important in relation to the synthesis of biologically active 2 -fluoro derivatives of nucleosides (see Section 111,4). Su and coworkers prepared the 2-triflates 236 and 239 through acid-catalyzed methanolysis of 3,5-di-O-benzyl-1,2-(9-isopropylidene-a-D-ribofuranose [to give 235 (major) and 238] and subsequent triflylation. On treatment with fluoride ion, the anomer 236 afforded exclusively the furan derivative 237, whereas the a anomer 239 gave the 2-fluoro compound 240... 

Deoxy-5 -fluoroadenosine (911) and the analogs 910, 912, 913 were prepared by coupling of 5-deoxy-5-fluoro-D-ribofuranose and 6-chloro-purine. 2, 5 -Dideoxy-5 -fluoroadenosine (914) was prepared through a displacement reaction of the corresponding 5 -0-tosyl precursor with fluoride (BU4NF in DMF). The carbocyclic nucleosides 915 and 916 have been prepared and their antiviral activities evaluated. 

Kalvoda149 studied the reaction of l-0-acetyl-2,3,5-tri-0-benzoyl-/3-D-ribofuranose (198) with various aromatic compounds in the presence of Lewis acids as catalysts, and prepared the corresponding D-ribofuranosylbenzenes, such as 199-201. It is of interest that an-omeric mixtures were sometimes formed under essentially uniform conditions, and it is not yet clear whether the a anomer arises from... 

Preparation of 5-(3-benzoylpropionyl)-3-deoxy-3-diisopropoxyphosphinylmethyl-l,2-di-0-acetyl-D-ribofuranose — Reaction of an alkyl bromide in a carbohydrate series with triisopropyl phosphite... 

A known method of acetalation by means of an enol acetate (2-acet-oxypropene),21 previously reported for some monosaccharides,22 has been reinvestigated.23 As it gave thermodynamically formed acetals in low to moderate yield (for instance, 30 and 54% yield, respectively, for the preparation of 2,3-O-isopropylidene-D-ribofuranose and 1,2 5,6-di-O-isopropylidene-a-D-glucofuranose), it appears to have no special advantages over the methods already available. 

Following a scheme similar to that described in Section 111,1, compounds having a complete D-ribofuranose structure and a ring-phosphorus atom were prepared.33,89... 

A useful modification of the Barton deoxygenation of secondary alcohols involves the use of O-phenylthionocarbonates developed by Robins et al. [15]. Application of this method for the generation and cyclization of a hex-5-ynyI radical is shown is Scheme 5. The precursors are readily prepared from D-ribose by a Grignard addition, followed by selective alcohol derivatizations. The major exo-isomer has been converted into carba-a-D-ribofuranose [16]. 

Townsend and coworkers (80JCS(P1)1853) prepared several ribofuranosyl nucleosides of the thieno[2,3-d]pyrimidine ring system by condensation of the silylated base with l-O-acetyl-2,3,5-tri-0-benzoyl-j3-D-ribofuranose in 1,2-dichloroethane in the presence of tin(IV) chloride (Scheme 101). These nucleosides are analogs of cytidine. Uridine analogs have been prepared from thieno[2,3-rf]pyrimidine-2,4-diones. 

D-Ribofuranose-type phospha sugars 50 (R=OH, Et, and Ph) and 2-deoxy-D-ribofuranose analogues 51 (R=OH and Me) in Fig. 3 have been prepared via longer reaction pathways by a similar ring closing intramolecular addition reaction of a P - H group to an aldehyde of sugars shown in Scheme 14 [17-20]. 

Dimethyl-D-ribose (XLIV) has been prepared by the hydrolysis of a tetramethyl-D-ribose dianhydride (XLIII) which is claimed to be a di-D-ribofuranose 1,5 5,1-dianhydride.49... 

In 1970, 1 was prepared by direct glycosylation of the silylated 5-azacytosine with acylated 1-halo sugars, but the yields were very low.20 In this procedure, 1,3,5-tri-O-acetyl-2-deoxy-D-ribofuranose (9) was converted into 3,5-di-0-acetyl-2-deoxy-D-ribofuranosyl chloride (10).21 The trimethylsilyl derivative of 5-azacytosine (11),22 prepared from 4-amino-6-pyrimidine by treatment with hexamethyldisilazane, was then allowed to react with intermediate 10 in acetonitrile over 7 days to give a mixture of anomers of l-(3,5-di-(9-acetyl-2-deoxy-D-ribofuranosyl)-5-azacytosine (12) in 10% overall yield. The anomeric mixture was treated with ethanolic ammonia to remove the acetyl groups. The resulting a and p anomers were separated by a combination of fractional crystallization and preparative layer chromatography on silica gel to give pure decitabine (1) and its a-anomer 13 in 7% and 52% yield, respectively. 

A 5-benzyl-D-ribose has been prepared by Kenner, Taylor and Todd,90 who etherified the methyl 2,3-isopropylidene-D-ribofuranoside (XXI) of Levene and Stiller91 with benzyl chloride to obtain methyl 2,3-iso-propylidene-5-benzyl-D-ribofuranoside (XXII), which was subsequently hydrolyzed to give amorphous 5-benzyl-D-ribose (XXIII). The structure of this ether was confirmed through acetylation to its triacetate (XXIV), hydrogenolysis to 1,2,3-triacetyl-D-ribofuranose (XXV) and further acetylation to the known, crystalline tetraacetyl-D-ribofuranose (XXVI). 

Preparation of 1-acetyl-5-0-benzoyl-2,3-dideoxy-3,3-difluoro-D-ribofuranose... 

More recently, the use of the chloroformate-aqueous alkali method has been revived by G. R. Barker and his associates in order to prepare a suitably protected D-ribose carbonate for a synthesis of a-D-ribofuranosyl phosphate. (An analogous synthesis of the latter compoimd, involving a phosgene-pyridine reaction, appeared almost simultaneously. ) Condensation of D-ribose with methyl chloroformate in the presence of aqueous sodium hydroxide led to the formation of a mixture of the anomers of l,5-di-0-(methoxycarbonyl)-D-ribofuranose 2,3-carbonate (LII), which was resolved by fractional recrystallization. The treatment of either of the derived D-ribofuranosyl chlorides with methanol and silver carbonate... 

In a previous investigation by the author (1) fluoro analogues of the current invention were prepared using 2,2,3,3-tetrafluorodiethyl butanedioate in Step 1 and the corresponding 2,2,3,3-tetrafluorofuran, (I), -ribofuranose, (II), and nucleoside derivatives, (III), respectively, were prepared. 

Reformatsky condensation of the reagent with ethyl bromod-ifluoroacetate afforded the 2,2-difluoro ester, which was further elaborated to the 2-deoxy-2-difluoro-L-ribofuranose. From there, various 2 -deoxy-2, 2 -difluoro-L-nucleosides were prepared (eq5). ... 

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