Synthesis of fluorinated analogues of acyclic nucleosides as potential antiviral agents

Abstract

In the search for more effective antiviral agents nucleosides and nucleoside analogues have been explored extensively.We report the synthesis of a number of acyclic analogues of guanosine, adenosine, and uridine fluorinated at different sites of the acyclic moiety.All compounds have been obtained in optically pure form by condensing chloromethyl 1,3-disubstituted-2-propyl ethers, chloromethyl 1,3-disubstituted-2-butyl ethers, and 1-chloroethyl 1,3-disubstituted-2-propyl ethers with the desired bases.Open chain fluoroalcohols, needed as starting materials, have been made available by elaborating homochiral fluorinated β-ketosulphoxides.Difluorinated molecules were obtained by DAST treatment of sulphoxide intermediates.In the nucleoside analogues 1 one or two fluorine atoms are present at the positions corresponding to the 3′ and 5′ carbon atoms of the sugar molecule. ▪