Author:

Keywords:

Adenosine, Adenosylhomocysteinase, Animals, Antiviral Agents, Humans, Hydrolases, Leukemia L1210, Mice, Microbial Sensitivity Tests, Stereoisomerism, Structure-Activity Relationship, Tumor Cells, Cultured, Science & Technology, Life Sciences & Biomedicine, Chemistry, Medicinal, Pharmacology & Pharmacy, S-ADENOSYLHOMOCYSTEINE HYDROLASE, HUMAN-IMMUNODEFICIENCY-VIRUS, HERPES-SIMPLEX VIRUS, POTENT, AGENT, RESOLUTION, CARBOVIR, 2'-DEOXYGUANOSINE, PHOSPHORYLATION, NUCLEOSIDES, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3214 Pharmacology and pharmaceutical sciences, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

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.