Of ribonucleosides

CH2(OMe)2, CH2 = CHCH2SiMe3, MeaSiOTf, P2O5, 93-99% yield." This method was used to protect the 2 -OH of ribonucleosides and deoxyribo-nucleosides as well as the hydroxyl groups of several other carbohydrates bearing functionality such as esters, amides, and acetonides. 

The CPTr group was developed for the protection of the 5 -OH of ribonucleosides. It is introduced with CPTrBr/AgN03/DMF (15 min) in 80-96% yield and can be removed by ammonia followed by 0.01 M HCl or 80% AcOH. It can also be removed with hydrazine and acetic acid. ... 

The pixyl ether is prepared from the xanthenyl chloride in 68-87% yield. This group has been used extensively in the protection of the 5 -OH of nucleosides it is readily cleaved by acidic hydrolysis (80% AcOH, 20°, 8-15 min, 100% yield, or 3% trichloroacetic acid). It can be cleaved under neutral conditions with ZnBrj, thus reducing the extent of the often troublesome depurination of A -6-benzyloxy-adenine residues during deprotection. Conditions which remove the pixyl group also partially cleave the THP group (t,/2 for THP at 2 -OH of ribonucleoside = 560 s in 3% Cl2CHC02H/CH2Cl2). ... 

The Cee group was developed for the protection of the 2 -hydroxyl group of ribonucleosides. 

The reduction of ribonucleoside triphosphates by various dithiols which are capable of intramolecular cyclization on oxidation (dihydrolipoate, dithioerythritol, dithiothreitol) yields 2 -deoxyribonucleoside triphosphates. These reactions also require 5-deoxyadenosylcorrinoids. 

REDUCTION OF RIBONUCLEOSIDE DIPHOSPHATES FORMS DEOXYRIBONUCLEOSIDE DIPHOSPHATES... 

Figure 34-5. Reduction of ribonucleoside diphosphates to 2 -deoxyribonucleoside diphosphates.

A wide variety of bases, nucleosides and nucleotides have been separated using porous layer bead ion exchangers. A representative chromatogram of the separation of ribonucleoside mono-phosphoric acids from the work of Smukler ( ) is shown in Figure 4. Recently, ion exchangers chemically bonded to small particle diameter (> 10 ym) silica have been successfully applied to the separation of nucleic acid constitutents (37). The rapid separations using such supports undoubtedly mean that they will find increasing use in the future. 

Figure 4. Separation of ribonucleoside monophosphofic acids. Conditions 250-cm anion exchange column gradient, 0.01M KHgPO containing HsPOi, (pH 2.6) to 0.15M KHiFO in 30 min column tempera-ture, 70 C detector, UV at 254 nm. 1, cyti-dine-S -monophosphoric acid 2, uridine-5 -monophosphoric acid 3, adenosine-5 -mon-ophosphofic acid 4, inosine-5 -monophosphoric acid 5, 3, 5 -cyclic adenosine mono-phosphoric add 6, guanosine-5 -monophosphoric acid (36).

Inhibition of ribonucleoside diphosphate reductase by hydroxyurea. Cancer Res 1968 28 1559-1565. 

The above complexes have been shown to mimic the second step of RNA hydrolysis as well, i.e. the-efficient cleavage of ribonucleoside 2, 3 -cyclic monophosphates [55] with bell-shaped pH-rate profile. With these substrates 37 showed much higher bimetallic cooperativity the dime/2 m0nomer ratios range between 64 and 457 for the different 2, 3 -NMPs used, while for 38 this ratio varies between 1 and 26. Since the mononuclear complexes have nearly the same activity toward the different 2, 3 -NMPs, these kinetic data indicate a notable base-selectivity of the dimer complexes. Since no correlation was observed with the size,... 

Tipson devoted most of his years in Levene s laboratory accomplishing seminal work on the components of nucleic acids. To determine the ring forms of the ribose component of the ribonucleosides he applied Haworth s methylation technique and established the furanoid structure for the sugar in adenosine, guanosine, uridine, and thymidine. He showed that formation of a monotrityl ether is not a reliable proof for the presence of a primary alcohol group in a nucleoside, whereas a tosyl ester that is readily displaced by iodide affords clear evidence that the ester is at the 5-position of the pentofuranose. Acetonation of ribonucleosides was shown to give the 2, 3 -C -isopropyl-idene derivatives, which were to become extensively used in nucleoside and nucleotide chemistry, and were utilized by Tipson in the first chemical preparation of a ribonucleotide, inosinic acid. 

Using guanosine or 2 -deoxyguanosine as starting material for the synthesis of ribonucleosides or deoxyribonucleosides respectively, the reaction can be driven towards completion by precipitation of the highly insoluble guanine co-product. This approach has... 

Deoxyrihonucleotides are generally formed by reduction of ribonucleoside diphosphates. This involves a series of redox reactions in which NADP+ and FAD play a role (see Section 15.1.1), with a subsequent electron transport chain. DNA contains thymine rather than uracil, so thymidine triphosphate (dTTP) is a requirement. Methylation of dUMP to dTMP is a major route to thymine nucleotides, and is dependent upon N, A °-methylenetetrahydrofolate as the source of the methyl group (see Box 11.13). 

Horvath, C. and Lipsky, S. R., Rapid analysis of ribonucleosides and bases atpicomole level using pellicular cation exchange resin in narrow bore columns. Analytical Chemistry 41(10), 1227-1234, 1969. 

Ferris, J. P. and Ertem, G. (1992). Oligomerization reaction of ribonucleosides on montmorillonite reaction of 5 -phosphorimidazolide of adenosine. Science, 257, 1387-9. 

Cory, J. G. (1989). Role of ribonucleotide reductase in cell division. In Inhibitors of Ribonucleoside Diphosphate Reductase Activity (J. G. Cory and A. H. Cory, eds.), pp. 1-16. Pergamon, New York. 

Purine nucleoside phosphorylase (PNP, E.C. 2.4.2.1) catalyzes the reversible phosphorylysis of ribonucleosides and 2 -deoxyribonucleosides of guanine, hypoxanthine, and related nucleoside analogs [1]. It normally acts in the phosphorolytic direction in intact cells, although the isolated enzyme catalyzes the nucleoside synthesis under equilibrium conditions. Figure 1 shows the chemical reaction. 

Z. and Liu, S.J. (1997) Rapid and highly selective cleavage of ribonucleoside 2, 3 -cyclic monophosphates by dinuclear Cull complexes. Angew. Chem., Int. Ed., 36, 2678-2680,... 

The greater hydrolytic lability of O-formyl than of O-benzoyl groups has been used in the preparation of ribonucleoside 2 -acetal 5 -esters.153 Acid-catalyzed reaction between 5,6-dihydro-4-methoxy-2//-pyran and N2-benzoyl-5 -0-benzoyl-3 -0-formylguanosine, followed by selective deformylation of the product with dilute methano-lic ammonia, gave N2-benzoyl-5 -0-benzoyl-2 -0-(4-methoxytetrahy-dropyran-4-yl)guanosine. 

The reaction catalyzed by polynucleotide phosphorylase differs fundamentally from the polymerase activities discussed so far in that it is not template-dependent. The enzyme uses the 5 -diphosphates of ribonucleosides as substrates and cannot act on the homologous 5 -triphos-phates or on deoxyribonucleoside 5 -diphosphates. The RNA polymer formed by polynucleotide phosphorylase contains the usual 3, 5 -phosphodiester linkages, which can be hydrolyzed by ribonuclease. The reaction is readily reversible and can be pushed in the direction of breakdown of the polyribonucleotide by increasing the phosphate concentration. The probable function of this enzyme in the cell is the degradation of mRNAs to nucleoside diphosphates. 

S. Chltfdek and J. Smrt, Oligonucleotidic compounds. V. 2 ,3 -0-alkylidene derivatives of ribonucleosides, Colt Czech. Chem. Common. 26 1301 (1963). 

M. J. Robins, J. S. Wilson, and F. Hansske, Nucleic acid related compounds. 42. A general procedure for the efficient deoxygenation of secondary alcohols. Regiospecific and stereoselective conversion of ribonucleosides to 2 -deoxynucleosides, J. Am Chem Soc. 105 4059 (1983). 

These were differently affected by different procedures. For example, when the enzyme was activated at 55°, the increment in ki was slight, but k2 increased 3.5-fold. Similarly, in the presence of EDTA, fc, and k2 values decreased independently, suggesting that the sites for both activities were different. Center and Behai (5) found that with the P. mirabilis enzyme, cyclic 2, 3 -UMP competitively inhibited the hydrolysis of bis(p-nitrophenyl) phosphate. The Ki was 40 pAf very close to the Km for the cyclic nucleotide (Km, 75 yM) which indicated that the two compounds could serve as alternate substrates being hydrolyzed at the same active site. In contrast, 3 -AMP was a mixed inhibitor of cyclic 2, 3 -UMP and bis(p-nitrophenyl) phosphate hydrolysis. Adenosine was a mixed inhibitor of bis(p-nitrophenyl) phosphate hydrolysis but a competitive inhibitor of 3 -AMP hydrolysis. From such kinetic studies Center and Behai (5) suggested that two separate and adjacent sites A and B are involved in the hydrolysis of the diester and phos-phomonoester substrates. Site A serves as a binding site for hydrolysis of ribonucleoside 2, 3 -cyclic phosphates and together with site B catalyzes the hydrolysis of the diester bond. During this reaction 3 -... 

Formylpurine thiosemicarbazone is a potent inhibitor of ribonucleoside diphosphate reductase and is active against herpes simplex and cytomegalovirus132), but is nephrotoxic. Attempts, so far unsuccessful, have been made to prepare derivatives which possess an antitumour effect but are less toxic133). 

Selective silylation of ribonucleosides.2 Only the 5 -hydroxyl group of ribonucleo-sides is silylated by reaction with the reagent in THF in the presence of silver nitrate. On addition of pyridine to the reaction, 2, 5 -disilyl derivatives are formed in 80-90% yield. The actual reagent may be r-butyldimethylsilyl nitrate. Highly selective 3, 5 -disilylation can be achieved in the presence of several silver salts (AgN03, AgC104, and AgOAc) in the presence of either DABCO or 4-nitropyridine N-oxide. 

Belikova, A.M., Zarytova, V.F. and Grineva, N.I. (1967) Synthesis of ribonucleosides and diribonucleoside phosphates containing 2-chloroethylamine and nitrogen mustard residues. Tetrahedron Lett., 37, 3557-3562. 

The other thiosemicarbazones are less well studied and as yet the link between antiviral action and chelation is not fully established. It has been proposed that the chelation of iron(II), a cofactor of ribonucleoside diphosphate reductase, could be the principal mode of action of the thiosemicarbazones300. However, other mechanisms are possible. Investigations of the ESR spectra of copper(II) complexes of thiosemicarbazones has been used to follow the intracellular reactions of the complexes - see Antholine et al.301 for a review. In Ehrlich cells the chelate becomes localized in the cell membrane302. This spectroscopic technique could also be used to monitor the antimala-rial action of 2-acetylpyridine thiosemicarbazones303. ... 

These two synthetic methods have, therefore, the built-in feature which limits them to the synthesis of aldoglycosyl nucleosides having a trans relationship between Cl and C2 substituents. From the practical point of view, however, in any successful synthesis of a D-ribofuranosyl analog of ribonucleosides, the /S configuration of the product is assured. In contrast, where the 2-acyloxy function is absent (as in poly-O-acyl-2-deoxyglycosyl halides), stereochemical controls of the condensation reaction, by the mechanisms involved in the trans rule, are lacking, and both the a and the /3 nucleoside should be formed.219... 

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