Synthesis and Antiviral Activity of 3’-Fluorocarbocyclic Oxetanocin A

Abstract

A new procedure for the synthesis of 3’-fiuorocarbocyclic oxetanocin A (lb) was developed. Addition of iodine fluoride to O-cyclohexylidene-cis-2-hydroxymethyl-3-methylene-l-cyclobutanol (4) afforded O-cyclohexylidene-(lS*,2S*,3R*)-3-fluoro-3-iodomethyl-2-hydroxyniethyl-l-cyclobutanol (5) and the undesired (lS*,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-[(lS*,2S*,3R*)-3-fluoro-3-iodomethyl-2-(trityloxymethyl)cyclobutyl]purine (10) was obtained as a sole addition product, which was readily converted to lb. This compound (lb) exhibited a broad spectrum of antiviral activity, especially against human cytomegalovirus. © 1995, The Pharmaceutical Society of Japan. All rights reserved.