represents a new class of potential anti-AIDS drugs. Synthetic approaches to this compound involving nucleophilic additions to a novel carbohydrate framework are discussed.
Acquired Immune Deficiency Syndrome (AIDS) has become the most important epidemic in modern time.
To date, the only proven strategy for the treatment of this disease is inhibition of viral replication, particularly, inhibition of the HIV reverse transcriptase . Recently a class of inhibitors of this enzyme, the 2',3'dideoxynucleosides ( e.g. ddC 1 and ddA 2) has been described. 1 The therapeutic use of these compounds, particularly ddA and other dideoxypurine nucleosides, however, is limited by their rapid degradation via hydrolysis of the sugar-base linkage. 2 To overcome this deficiency we have designed a modified dideoxynucleoside (Iso-ddA, 3) in which a more stable nucleoside linkage exists. The exchange of oxygen and carbon atoms, while maintaining an isomeric relationship with the model compounds, should impart stability at the sugar-base union. Herein we describe the synthesis, stability and x-ray structure of iso-ddA, a member of a novel class of inhibitors of HIV replication.