Methylene-gem-difluorocyclopropane analogues of nucleosides: Synthesis, cyclopropene-methylenecyclopropane rearrangement, and biological activity

Alkylation-elimination of adenine and 2-amino-6-chloropurine with gem -difl uorocyclopropane dibromide 10 gave E- and Z-methylene-gem-difluorocycloprop anes 11a, 11b, 12a, and 12b and gem-difluorocyclopropenes 13a and 13b. Debe nzylation of intermediates 11a, 11b, 12a, and 12b afforded E- and Z-methyle necyclopropanes 4a, 4b, 5a, and 5b. Hydrolysis of 2-amino-6-chloropurine de rivatives 4b and 5b afforded guanine analogues 4c and 5c. Composition of pr oducts (except 14b) obtained from alkylation-elimination reflects thermodyn amically controlled cyclopropene-methylenecyclopropene rearrangement. The E -isomer 4a was moderately active against human cytomegalovirus and along wi th the Z-isomer 5a was active against leukemia L1210 and solid tumors in vi tro.