Modifications of the Nucleoside

The chemical modification of the cytotoxic nucleosides ara-C, 5-FdU, ETC, and correspondingly of the antiviral nucleosides azidothymidine (AZT), dideoxycytidine (ddC) and dideoxyinosine (ddl) and their formulation in liposomes render these new heterodinucleoside compounds interesting candidates for further developments. 

R. Ranganathan, Modification of the 2 -position of purine nucleosides Syntheses of 2 -a-substituted-2 -deoxyadenosine analogs, Tetrahedron Lett. p. 1291 (1977). 

Figure 15.3 Nucleotides that have been spin-labeled by postsynthetic modification of the oligomer at either the base (A), the sugar (B), the internal phosphodiester (C), or the terminus (D). B indicates the nucleoside base.

Simple modification of the Yoshikawa phosphorylation allows the synthesis of (1-thio) triphosphates (a-thiotriphosphates) (Protocol 12). The initial phosphorylation with thiophosphoryl chloride is slower than that using phosphoryl chloride and requires the addition of 2,4,6-collidine as a catalyst for the pyrimidine nucleosides.7 Protocol 12 is intended for pyrimidine nucleosides on a 0.2 mmol scale and should be modified where indicated for purine nucleosides. The diaste-reoisomers of nucleoside (l-thio)triphosphates can be distinguished by both 31P NMR (the signal for the a-phosphate of the Sp diastereoisomer is down-field relative to that of the Rp diastereoisomer) and reversed-phase HPLC (the Sp diastereoisomer elutes first). Preparative separation can also be achieved using the latter method (see Protocols 21-23).17... 

The synthesis of nucleoside diphosphates is best achieved using the Poulter reaction,9 which involves reaction of the tris(tetra-n-butylammonium) salt of pyrophosphate with a nucleoside 5 -tosylate in acetonitrile. A general procedure for the synthesis of nucleoside tosylates of thymidine and 2 -deoxyadenosine is included (Protocol 15), whilst the syntheses of the other tosylates (including ribonucleosides) have been described using related procedures. Simple modification of the protocol, whereby the tetra-n-butylammonium salt of pyrophosphoric acid is replaced by methylene or difluomethylene bis phosphonate, allows the synthesis of hydrolytically stable dNTP analogues.10... 

Fluoropurin-8-amine nucleosides have also been prepared by appropriate modification of the Schiemann reaction, e.g. formation of 4. ... 

Nucleoside dimers linked by the butadiynediyi group were prepared by A. Burger et al. using the Eglinton modification of the Giaser coupiing via dimerization of 3 -C-ethynyl nucleosides. ... 

From this brief survey, it is seen that there were few features of carbohydrate metabolism in plants that escaped Hassid s touch, and much that we now know about the role of sugar nucleotides in the interconversion of carbohydrates in plants is a direct result of his persistent effort. From the incorporation of labelled precursors into monosaccharides, to the conversion of the monosaccharides into their glycosyl phosphates, to the action of the pyrophosphorylases in the synthesis of glycosyl esters of nucleoside pyrophosphates, to the interconversion of the resulting sugar nucleotides, to the polymerization of the activated monosaccharides to yield disaccharides and the homopolysaccharides, and, finally, to the modification of the polysaccharides by methylation—in summary, to almost every aspect... 

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