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.