Stereospecific synthesis and antiviral properties of different enantiomerically pure carbocyclic 2'-deoxyribonucleoside analogues derived from common chiral pools: (+)-(1R,5S)- and (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one.
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 stereospecific 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 micrograms/mL, respectively] and HSV-2 (MIC: 2 and 20 micrograms/mL, respectively), but virtually inactive against TK- HSV-1 (MIC: 40 and 100 micrograms/mL, respectively). (+)-Carbathymidine was also active against vaccinia virus (2 micrograms/mL). None of the compounds had a specific effect on the replication of HIV or other RNA viruses.
Béres
J
J
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Sági
G
G
Tömösközi
I
I
Gruber
L
L
Baitz-Gács
E
E
Otvös
L
L
De Clercq
E
E
D000998:Antiviral Agents / Q000138:chemical synthesis*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D008826:Microbial Sensitivity Tests; D018139:Simplexvirus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014616:Vaccinia virus / Q000187:drug effects
D000998:Antiviral Agents; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; C063781:carbathymidine; D013936:Thymidine