C-Nucleosides: Synthesis of Novel Ribavirin Analogues by Cycloaddition Reactions of D-Allononitrile-N-sulfide

Article abstract of DOI:10.1021/jo00186a017

The preparation and synthetic application of O-benzoyl-protected 2,5-anhydro-D-allononitrile-N-sulfide was investigated.The O-benzoyl-protected 2,5-anhydro-D-allononitrile was hydrolyzed to the corresponding allonamide, which was converted to the protected 5-β-D-ribofuranosyl-1,3,4-oxathiazol-2-one.Generation of the nitrile sulfide by pyrolysis of the latter in the presence of ethyl cyanoformate and ethyl propiolate afforded thiadiazole and isothiazole carboxylate esters, which were elaborated to thiadiazole and isothiadiazole C-nucleoside analogues 3 and 4 of ribavirin.None of these compounds produced any significant inhibition either of in vitro L1210 cell growth or of viral replication in any of the tested systems.Analysis of the 1H NMR spectra of ribavirin and the C-nucleoside analogues 3 and 4 showed that the conformational equilibrium of the ribose moiety, which lies at the N side for ribavirin, is shifted toward the S conformers in the compounds 3 and 4.Ribavirin and compound 4 have a similar rotameric distribution at the C_4'-C_5' exocyclic bond, but compound 3 behaves differently.