Ribofuranose nucleosides

The most important derivatives of pyrimidines and purines are nucleosides Nucleosides are N glycosides m which a pyrimidine or purine nitrogen is bonded to the anomeric carbon of a carbohydrate The nucleosides listed m Table 28 2 are the mam building blocks of nucleic acids In RNA the carbohydrate component is d ribofuranose m DNA It IS 2 deoxy d ribofuranose... 

Hydantocidin. Hydantocidin (182), C2H2QN2O3, is elaborated by S. hygroscopicus (278). It is unique in that the anomeric carbon of the ribosyl moiety forms the spHo bond of hydantoin (279). The ribofuranose moiety which has been reported to be in a Q -endo conformation (279) has been synthesized (280,281). Hydantocidin is a herbicidal nucleoside with activity against monocotyledenous and dicotyledenous plants. 

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. 

Any discussion of the prebiotic phosphorylation of nucleosides must take into account the probably neutral or alkaline conditions in a prebiotic environment. Some model phosphorylating systems have been studied, for example, the synthesis of /S-o-ribofuranose 1-phosphate from ribose and inorganic phosphate in the presence of cyanogen. Sodium trimetaphosphate will phosphorylate cw-glycols in good yield under alkaline... 

Esterification of 5 -nucleoside derivatives with N-(aminoacyl)-imidazoles yields 2 - and 3 -(aminoacyl) derivatives and proceeds with apparently little selectivity169,170 this is not surprising in view of the facile, base-catalyzed, ester migration that may occur in 2 (3 )-esters of the D-ribofuranose system (see Section VII,1). 

Scheme 18.55 Further allenic nucleoside analogs with a modified ribofuranose ring.

Figure 9.13 A glycosylamine. Adenosine is a nucleoside and is an example of a glycosylamine in which the nitrogen atom of the purine, adenine, is linked directly to carbon 1 of /3-D-ribofuranose.

Nature has exploited ribose derivatives for a number of cmcially significant biochemicals. Many of these contain a heterocyclic base attached to the P-anomeric position of o-ribofuranose, and are termed nucleosides. Adenosine, guanosine, cytidine, and uridine are fundamental components of ribonucleic acids (RNA see Section 14.1),... 

Two ciT-dihydroxylation reactions of alkenes formed steps in the synthesis of the antiviral drug (-)-oseltamvir ( tamiflu ) were carried out with RuO /aq. Na(IO )/ EtOAc-CH3CN/4°C [169]. Terminal alkene groups in nucleosides were oxidised to alcohols by RuClj/aq. Na(lO )/EtOAc-CH3CN/0°C thus 3,5-di-0-benzyl-l,2-di-O-isopropylidene-3-C-vinyl-a-D-ribofuranose (1) gave the diol (2) which, on cleavage with Na(lO ) and reduction with NaBH yielded 3,5-di-0-benzyl-l,2-di-O-isopropylidene-3-C-hydroxy-methyl-a-D-ribofuranose (3) (Fig. 3.4) [170]. 

SnCl4-catalyzed glycosylation of l-(trimethylsilyl-4-trimethylsilyloxy)-l//-pyrazolo[3,4-d]pyrimidine (254) with acylated ribofuranose gave the nucleosides 255 and 256 (81CB1610). 

Nucleosides are glycosides of ribofuranose or deoxyribofuranose whose aglycones are pyrimidine or purine bases. The bases are bonded to C of the sugar. 

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. 

Fusion of the base 306 with l,2,3,5-tetra-0-acetyl-/3-D-ribofuranose (307) in the presence of I2 catalyst gave a mixture of nucleosides (308-311) in low yields. Better yields were obtained by thionation with phosphorus penta-sulfide of the oxo derivatives, 4-(2, 3, 5 -tri-0-acetyl-/3-D-ribouranosyl)-... 

Most naturally occurring nucleosides and nucleotides contain a ribofuranose moiety, From detailed 13C NMR studies of carbohydrates [88, 89, 696] it is known that primary CH2OH groups resonate at higher field than the secondary ring CHOH groups, and thus... 

Fig. 3-1. Structure of two nucleosides, 1, Uridine and 2, guanosine, which both contain /3-D-ribofuranose residue. The aglycon part is derived from a pyrimidine and purine base, respectively.

The crystal structures of the important ribofuranoses or 2-deoxy-ribofuranoses have not been determined, since these forms are in the minority with respect to the pyranoses in solution. There are numerous examples, however, in the crystal structures of the nucleosides and nucleotides. Those that contain the ribofuranose moieties quite commonly display vicinal 0(2 )H 0(3 ) or O(30H 0(2 ) intramolecular hydrogen bonding as the minor component of a three-center bond. This type of hydrogen bonding is described in Part IB, Chapter 9. 

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. 

In contrast to various syntheses of 1,2,3-triazole nucleosides by cycloaddition of glycosyl azides to substituted alkynes (see Section 4.11.5.2.2 and e.g. (7ojhci269)), the acid-catalyzed fusion of methyl l,2,3-triazole-4-carboxylate, 4-cyano-l,2,3-triazole and 4-nitro-l,2,3-triazole (156) with an acylated ribofuranose provides the corresponding 4-substituted 2/3-D-ribofuranosyl-l,2,3-triazoles (157) along with the l-/3-D-isomers (158) (72jhcii9s). 

Persilylated intermediates such as 170 are also obtained during nucleoside synthesis. Thus, reaction of 3,5-bis-(trimethylsilyloxy)-l,2,4-triazine (168) with l-0-acetyl-2,3,5-tri-0-benzoyl-/8-D-ribofuranose (169) in the presence of 0.76 equivalents of SnCU in 1,2-dichloroethane leads to 170 as intermediate, which reacts with a 10-fold excess of pyrrolidine to give 0-benzoylated 6-azacytidine (171) in 57% yield (75LA988). Inosine (172a), guanosine (172b), or xanthosine (172c) have hitherto been trans-... 

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