Synthesis and antiviral activity of 3'-fluorocarbocyclic oxetanocin A.
A new procedure for the synthesis of 3'-fluorocarbocyclic oxetanocin A (1b) was developed. Addition of iodine fluoride to O-cyclohexylidene-cis-2-hydroxymethyl-3-methylene-1-cyclobutanol (4) afforded O-cyclohexylidene-(1S*,2S*,3R*)-3-fluoro-3-iodomethyl-2- hydroxymethyl-1-cyclobutanol (5) and the undesired (1S*,2S*,3S*)-isomer (6) in 6.2% and 38% yields, respectively. When fluorine was introduced into the carbocycle after condensation of 6-chloropurine, 6-chloro-9-[(1R*,2S*,3R*)-3-fluoro-3-iodomethyl-2- (trityloxymethyl)cyclobutyl]purine (10) was obtained as a sole addition product, which was readily converted to 1b. This compound (1b) exhibited a broad spectrum of antiviral activity, especially against human cytomegalovirus.
Sato
Y
Y
Department of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Maruyama
T
T
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D010948:Viral Plaque Assay
D000998:Antiviral Agents; C051061:oxetanocin; D000225:Adenine