The primary alcohol of cis-3-hydroxy-4-cyclohexenylcarbinol was protected with a silyl group and then the configuration of the secondary alcohol was inverted (using Mitsunobu conditions, followed by deacylation). The secondary alcohol was converted to a carbonate, which, in turn, was converted to 6-chloropurine derivatives, using palladium coupling conditions. A modified deprotection procedure gave the free alcohol of these acid/base sensitive nucleoside analogs. The resulting 6-chloropurine derivatives were treated with ammonia, giving the 6-aminopurine derivatives which were finally converted with adenosine deaminase to the guanosine and inosine analogs.
Bibliographical noteFunding Information:
We wish to thank Mr. Jay Brownell for conducting the P-388 mouse leukemia cytotoxicity studies, the HSV-1 antiviral studies, and for help with the adenosine deaminase reactions. This work was supported by Public Health Service Grant CA23263 from the National Cancer Institute.