This work continues to generate a series of new cyclopentenyl (CPE) nucleoside isosteres that are being studied as antitumor or antiviral agents. The discovery of the remarkable antitumor and antiviral activity of the cytosine analogue (CPE-C) has prompted an extensive investigation into this type of carbocyclic nucleoside. During this endeavor, new improved methods of synthesis and protection-deprotection procedures have been investigated and adapted to the chemistry of the CPE series. The ara and 2'-deoxy analogues of CPE-C were synthesized. Ara-CPE- C is active against the Influenza A2 virus, but neither compound has antitumor activity. Additional amounts of CPE-U were synthesized for in vivo studies of the inhibition of the pyrimidine salvage pathway. The active metabolite of CPE-C (its 5'- triphosphate) also was synthesized and identified as a potent inhibitor of cytidine triphosphate synthetase. Among the cyclopentenyl purine compounds, 3-deazaneplanocin, a potent inhibitor of S-adenosylhomocysteine hydrolase, has excellent antiviral activity against both RNA and DNA viruses without the high level of cytotoxicity normally associated with the parent fermentation product, neplanocin.
