Synthesis of non-steroidal 2-methoxyestradiol mimetics based on the bicyclo[3.3.1]nonane structural motif

Two pairs of bicyclo[3.3.1]nonane derivatives with 2-methoxyphenol moiety were synthesized as non-steroidal 2-methoxyestradiol mimetics demonstrating noticeable cytotoxicity to human lung carcinoma cell line A549. Compounds with 2-methoxyphenol annulated with bicyclo[3.3.1]nonane fragment were obtained using BF₃-assisted oxirane opening in 5-(4-benzyloxy-3-methoxyphenyl)-1-oxaspiro[2.5]octanes with simultaneous intramolecular cyclization and reduction as the key step. endo-7-Hydroxybicyclo[3.3.1]nonane-exo-3-carboxylic acid was converted into two esters containing 2-methoxyphenol fragment in either acid or alcohol part of the molecule.