Antiviral enantiomeric preference for 5'-noraristeromycin.
In order to determine if the potent antiviral properties of (+/-)-5'-noraristeromycin reside in one of its enantiomers, an analysis of each enantiomer has been carried out. A five-step route to the (+)-stereoisomer is described from (+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate, whereas the synthesis of the (-)-enantiomer had been reported previously from the same starting material. The (-)-2 and (+)-2 enantiomers were evaluated for antiviral activity against a large number of viruses and found to display an antiviral activity spectrum characteristic of (S)-adenosyl-L-homocysteine hydrolase inhibitors. The (-)-enantiomer retained the significant anticytomegalovirus properties previously reported for the racemic 2 and was, on the average, 10-fold more potent than (+)-2 in inhibiting virus replication, tumor cell growth, and (S)-adenosyl-L-homocysteine hydrolase activity.
Siddiqi
S M
SM
Department of Chemistry, University of South Florida, Tampa 33620-5250.
Chen
X
X
Schneller
S W
SW
Ikeda
S
S
Snoeck
R
R
Andrei
G
G
Balzarini
J
J
De Clercq
E
E
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000998:Antiviral Agents; C076829:5'-noraristeromycin; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine