Sugar modified nucleosides

The fragmentation of base-modified nucleosides related to cytokinin and sugar-modified nucleosides, mainly cyclo- and T- and 3 -chloro derivatives,has been reported. However, all of the El-induced reactions discussed in these reports have already been presented above. Although they do not introduce any new fragmentation pathways, both reports present a... 

Table 11.3-8. Nucleoside phosphorylase-catalyzed synthesis with various heterocycles as acceptors or sugar-modified nucleosides as donors.

Advances in synthesis of sugar-modified nucleosides in past 10 years 01YGK331. 

The activities of these multifunctional enzymes can be employed for purposes of producing various base- and sugar-modified nucleosides, nucleotides and poly(oligo)nucleotides. The advantage arising from the multifunctionality is that entire reaction sequences, as occuring with high efficiency in vivo, can be carried out in vitro with the aid of such an enzyme. ... 

Structures of a range of base and/or sugar-modified nucleoside analogues have been described. The 6-azacytosine 71, pyrazolo[3,4-/>]quinoline P-ribo-furanoside 72 5 -0-benzoyl-3 -deoxy-2 -keto-a-uridine, 3 -deoxy-3 -5-(2-nitrophenyldisulfanyl)thymidine, ° anhydronucleoside 73, 5-adamantyl-2 -deoxy-4 -thio-a-uridine, the bicyclic nucleoside analogue 74, and bicyclic analogues 75 (both epimers) and 76. ... 

Modification other atoms or groups. Besides fluorine atoms, other atoms (such as C, N and O) and groups are also used to produce novel sugar-modified nucleoside monophosphates. 2-C-Methyl nucleosides are potential candidates with activity against Hepatitis C virus. Leisvuori et al ° prepared 3,5-cyclic phosphates (25a) and 3,5-cyclic thiophosphates (25h) of 2-C-methyl ribonucleosides as potential antiviral drugs. 

Locked nucleic acids (LNA) are a modified RNA in which the ribose moiety is modified with an extra bridge connecting the 2 -0 and 4 -C atoms. Thus LNA nucleosides can be regarded as sugar-modified nucleosides. Madsen et al. synthesized the 2 -amino-LNA phosphoramidites... 

Based on these successes, several base- and sugar-modified nucleoside analogs bearing a triazole group at various positions have been prepared and evaluated. 

In recent year s, clinical studies on the role of uiinai y luodified nucleosides as the biochemical mai kers of various types of cancer have been actively undertaken. Most of the urinai y modified nucleosides ai e piimai ily originated by methylation of either the base part, the sugar hydroxyl par t, or in some cases, both par ts of the course of biodegradation of tRNA molecules. Hence, their isolation and identification plays a major role in biochemical analysis. 

The recognition of a molecular species ion in a spectrum may be difficult. Hence, a scan of neutral losses with mass 132 Da allows one to detect selectively the protonated molecular ions of the various nucleosides contained in the mixture, because the production of an intense BH2+ ion from MH+ by the loss of a sugar molecule (132 Da for a ribose) is an important characteristic of positive ion spectra. A modified nucleoside, /V6-isopentenyladenosine, was identified in tRNATyr of E.coli using this method [210] (Figure 8.39). 

The bottom edge of the sugar ring has been done away with so that a simple alkyl chain remains. This compound has proved amazingly successful as an antiviral agent and It Is highly likely that more modified nucleosides will appear In the future as Important drugs. 

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