Stereospecific synthesis and antiviral properties of different enantiomerically pure carbocyclic 2'-deoxyribonucleoside analogs derived from common chiral pools: (+)-(1R,5S)- and (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one

Abstract

Enantiomerically pure (+)- and (-)-carbocyclic thymidine, (-)-carbocyclic 3''-epi-thymidine, (+)-carbocyclic 3''-deoxy-3''-azidothymidine, (+)-carbocyclic 2,3''-O-anhydrothymidine, (+)-carbocyclic 3''-O,6''-methylenethymidine, and (+)-(6''S)-carbocyclic 6''-methylthymidine were synthesized in a stereospecfic manner from common chiral pools of (+)-(1R,5S)- and (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one and evaluated for antiviral activity. (+)-Carbathymidine and, to a lesser extent, (+)-carbocyclic 2''-deoxyadenosine proved to be effective against HSV-1 [minimum inhibitory concentration (MIC): 0.2 and 2 .mu.g/mL, respectively] and HSV-2 (MIC: 2 and 20 .mu.g/mL, respectively), but virtually inactive against TK- HSV-1 (MIC: 40 and 100 .mu.g/mL, respectively). (+)-Carbathymidine was also active against vaccina virus (2 .mu.g/mL). None of the compounds had a specific effect on the replication of HIV or other RNA viruses.