Modification of the Sugar

As modified oligonucleotides have become a major field of investigation for chemists, methods for the suitable protection/deprotection applied to the synthesis of nucleoside monomers have become equally important. Selective protection of a multifunctional compound is a challenging problem in organic synthesis. In nucleoside chemistry, selective manipulation of the hydroxyl groups on the carbohydrate moiety over amino groups of the bases is synthetically challenging and 

This first section wiU study different regjoselective processes of several types of nucleosides depending on the lipase used. Application of biotransformations over these compounds has acquired great importance in order to prepare new derivatives with interesting pharmacological activities. Two lipases, namely, Candida antarctica type B (CALB) and Pseudomonas cepacea, free (PSL) or Pseudomonas cepacea, immobilized (PSLC), are selective towards one of the two hydroxyl groups of different 2 -deoxynucleosides. Thus, it is possible to prepare the acylated compounds in S -position with CALB [10], whereas PSL is selective towards the secondary hydroxyl group [11]. Vinyl or oxime esters can be used as acyl donors. 

This enzymatic alkoxycarbonylation is of great utUity in activating hydroxyl groups 

It has been described that, in some cases, the acylation of one hydroxyl group of the sugar moiety in a nucleoside derivative can increase its biological activity 

In addition, regioselective enzymatic acylation of pyrimidine 3, 5 -diaminonu-deoside derivatives is possible depending on the biocatalyst employed in the process [28]. N-5 -Acylated products were obtained using CALB as a biocatalyst, whereas PSLC was selective towards the N-3 position. Molecular modeling studies 

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For this purpose, we cleaned the lower than 1000 cm and higher than 1500 cm" areas by subtracting the Raman spectrum of the solvent (see Analysis Methods) in order to make some possible modifications of the sugar-phosphate part of DNA upon complexation conspicuous. Furthermore, we could expect to refine the nature of the weak interactions of SOAz with DNA b s by observing the low frequencies characteristic of these bases. 

Except for this particular example, quantitative deprotections were observed for other sugar nitrates without modification of the sugar moiety. Some other Al-deriva-tives such as diphenyl hydrazino substituents introduced by triflate displacement at the C-6 position of galactose residues were photolyzed but in low yields [112]. This group remains of limited interest for any further use in synthesis. 

S. Ogawa and D. Aso, Chemical modification of the sugar moiety of methyl acarviosin synthesis and inhibitory activity of eight analogues containing a 1,6-anhydro bridge,... 

The syntheses of the 6 -0-(bromopentyl)-substituted allofuranosyl-purine and -pyrimidine phosphoramidite (40a-c) and the 2 -0-[(3-bromopropoxy)methyl] substituted allofuranosyl-purine and -pyrimidine phosphoramidite (41a-c) have been reported. Such modifications of the sugar moiety presented opportunities for the functionalisation of oligonucleotides with a variety of soft nucleophiles while the fully protected sequence was still on the solid support. ... 

It would seem reasonable that, with proper protection of the phosphoric group, sulfonylation of nucleotides will gain wider utility as a method for the modification of the sugar moieties in these compounds. 

Unlike dehydrogenases, enzymes cleaving the glycosyl bond are extremely sensitive to modifications of the sugar moiety. The arabino analogs, arabino-NAD+ and 2 -fluoro-araW/K>-NAD (12) are both potent, slow-binding competitive inhibitors of calf spleen NADase with ATj values of 170 nAf and 2 fiM,... 

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