Among the new cyclopentenyl nucleosides synthesized and evaluated as antitumor and antiviral agents, 5-aza-cyclopentenylcytosine (5-aza-CPE-C) and the 2-oxopyrimidine analogue (CPE-Z) displayed no biological activity. In the purine series, the carbocyclic psicose analogue, psicoplanocin A, had marked activity against RSV, measles, and parainfluenza viruses. This activity is consistent with a mechanism of action similar to that of neplanocin A. The synthesis of (-)-carbodine, an antitumor cyclopentyl nucleoside previously reported in the literature as a racemate, was achieved from cyclopentenyl, cytosine (CPE-C). The isomeric compound (-)-isocarbodine was also synthesized. (-)-Carbodine was ca. twofold more potent than the racemate. (-)-Isocarbodine was unexpectedly effective against human influenza virus. Several new cyclopentenyl nucleosides inspired by two natural products neplanocin A and clitocine, have been synthesized. Their biological evaluation is in progress. The synthesis of the cyclopentenyl nucleoside analogue of the antitumor drug tiazofurin is near completion. 3-Deazaneplanocin A has shown potent activity in vitro against the African swine flu virus, as well as synergistic activity with ribavirin against the measles virus. This compound is also active in vivo against the Ebola virus in the SCID mouse model.
