Five-membered rings nucleosides

The ring-open product is written here as an enediol, which is able to recyclize in an aldol condensation (step V) to form a five-membered ring with a branch at C-3. The l-streptosyl nucleoside diphosphate formed in this way serves as the donor of streptose to streptomycin. 

The marked stereoselectivity of these radical reactions must be ascribed to the effect of the bulk of the protecting groups. However, the radicals that were manipulated may have also shown an anomeric effect due to the vicinal oxygen. In a furanose sugar it is not easy to evaluate the anomeric effect without ESR, and also, the molecules concerned have two fused five-membered rings. This fixes the conformation into a V-shape. Such molecules are well known to have exo-reactivity and the formation of endo-bonds is difficult. All these effects may be acting together to make this nucleoside chemistry especially stereospecific. 

There have been relatively few reports concerning the chemistry of fused 5-6 bicyclic systems with one heteroatom in the five-membered ring and three in the six-membered ring, so this is a field of chemistry which is very open to new research. The only classes of compounds which have been widely reported are the S -nucleoside cyclic phosphates (1) and their analogues. Many thousands of papers have been written concerning these molecules in contrast to the very small number... 

Murray-Rust and Motherwell [35] searched the CSD for all y8-l -aminofuranoside fragments (12) in nucleosides and nucleotides and made a principal component analysis of the conformations found for the five-membered ring and its direct substituents. A detailed description of this analysis is given in Chapter 4, Section 4.6.3.1. Here we merely summarize the results. 

Other important members of this class of nucleoside analogues are those that contain an oxathiolane ring system, in particular, the cytosine derivative, BCH-189. This compound showed potent anti-HIV activity. Again it was observed that the five-membered ring system of... 

Figure 2.19) exhibited the most potent antiviral activity among the evaluated five-membered ring heterocycles (1,2,4-triazole and imidazole) carbocychc nucleosides (Figure 2.20 and Table 2.12). 

The discovery of clinically relevant nucleoside analogs, such as Ribavirin [7], Viramidine [8], or AICAR [9], containing a 1,2,4-triazole or an imidazole ring as nucleobase has led to an intensive search for new five-membered ring base-modified nucleoside analogs including 1,2,3-triazole derivatives (Figure 10.2)... 

The Wittig reaction, or its phosphonate modification, can be a very useful reaction in the synthesis of anomerically functionalized precursors to C-nucleosides, particularly when the ring-closure reaction leads to five-membered, anhydro derivatives, and occurs with a high degree of stereocontrol. Zhdanov and coworkers,130 showed that the following five-membered, Wittig products (179-182) were formed from various free sugars and (p-methoxybenzoyl)- and (acetyl-methylene)-triphenylphosphoranes. 

The number of five-membered heterocycles with four hetero atoms is limited to those with nitrogen atoms. Thus, the tetrazole acyclonucleo-sides were formed from sugars N,N -diphenylformazanes by the action of AT-bromosuccinimide or lead tetraacetate [133,134]. The synthesis of the tetra-O-benzoyl-D-lyxononitrile and its conversion to (o-lyxo-tetritol-l-yl)-tetrazole derivatives upon reaction with sodium azide was reported [133, 134]. A pseudo C-nucleoside including a tetrazole ring was achieved by conversion of 3- 0-benzyl- 1,2-O-isopropylidene-D-ribo-pentodialdehydo-1,4-furanose to the respective nitrile and then reaction with sodiiun azide [86]. 

Saturated heterocyclic six-membered rings are much less flexible than their five-membered counterparts [46]. The activation energy barrier for the conversion of one chair form of cyclohexane into the alternate form is ca. 42 kJ/mol [47,48]. The activation energy for the interconversion barrier between the two puckered conformations, i.e., N- and S-type pseudorotamers, of the pentofuranose moiety in purine nucleosides is much smaller in comparison, i.e., below 20-25 kJ/mol. 

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