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

Alkylation−elimination of adenine and 2-amino-6-chloropurine with gem-difluorocyclopropane dibromide 10 gave E- and Z-methylene−gem-difluorocyclopropanes 11a, 11b, 12a, and 12b and gem-difluorocyclopropenes 13a and 13b. Debenzylation of intermediates 11a, 11b, 12a, and 12b afforded E- and Z-methylenecyclopropanes 4a, 4b, 5a, and 5b. Hydrolysis of 2-amino-6-chloropurine derivatives 4b and 5b afforded guanine analogues 4c and 5c. Composition of products (except 14b) obtained from alkylation−elimination reflects thermodynamically controlled cyclopropene−methylenecyclopropene rearrangement. The E-isomer 4a was moderately active against human cytomegalovirus and along with the Z-isomer 5a was active against leukemia L1210 and solid tumors in vitro.