A series of C-nucleoside analogs pyrimidine N-nucleosides, which exhibit significant activity against the AIDS virus human immunodeficiency virus (HIV, will be prepared six C-nucleosides, C-AZT, C-dThd, C-deThd, C-AZC, c-dCyd and C-deCyd which are analogs of corresponding N-nucleosides of thymidine and cytidine which have been shown to be potent and selective inhibitors of HIV and, specifically, of the HIV reverse transcriptase. Synthesis of the target compounds will be accomplished using chemistry developed during the past decade in the Principal Investigator's laboratory in which a glycal (1,2-unsaturated carbohydrate) is coupled in a regio- and steriospecific manner with a pyrimidine aglycone derivative in the presence of palladium acetate. Reactions already demonstrated lead directly to both the 2'-deoxy- and 2'3-dideoxydedehydro- classes of pyrimidine beta-C- nucleosides for the proposed syntheses. The target pyrimidine C-nucleosides are expected to exhibit activities against the AIDS virus equal to or greater than those of the corresponding N-nucleoside analogs presently available. The C-nucleosides have the advantage that they are not subject to degradation by pyrimidine nucleoside phosphorylases.
