Synthesis of 2, 16α- and 4, 16α-[16α-18F]difluoroestradiols and their 11β-methoxy derivatives for estrogen receptor imaging

We have prepared the 2- and 4-fluoro derivatives of 16α-[18F]fluoroestradiol (FES) (4a, b) and 11β-OMe-FES (4c, d). Electrophilic substitution of estrone or 11β-OMe-estrone with N-fluoropyridinium salt gave the 2-and 4-F derivatives 1, which were converted to the triols 2 and subsequently to the reactive 16β, 17β-cyclic sulfates 3. Stereoselective opening of the cyclic sulfates via nucleophilic fluorination with Me4NF or [18F]F- and removal of the protecting ether and sulfate groups via rapid acid hydrolysis gave 4a-d or [16α-18F]-(4a-d).