Synthesis and properties of novel nucleoside and nucleotide analogues : a thesis

The synthesis of novel nucleoside and nucleotide analogues in which the sugar moiety is replaced by an aliphatic chain is described. The acyclic analogue of adenosine was tested as both a substrate and an inhibitor of adenosine deaminase while the interaction of some dinucleoside monophosphate analogues with spleen and snake venom phosphodiesterase is reported. Some mention is made of the solution conformation of these acyclic derivatives.The utility of the methyl group as a phosphate protecting group in oligonucleotide synthesis was reinvestigated and the preparation of some interesting 2', 5' linked trinucleoside diphosphate analogues of adenosine, with the methyl moiety as phosphate masking group, was undertaken. A novel approach to the cleavage of phosphate methyl esters is discussed.A facile fluoride ion mediated preparation of alkylated nucleoside base fragments was discovered. This procedure led to high isolated yields of a variety of N-alkylated purines and pyrimidines