Synthesis, receptor binding, and tissue distribution of (17α,20E)- and (17α,20Z)-21-[125I]Iodo-19-norpregna-1,3,5(10),20-tetraene-3,17-d ol

Article abstract of DOI:10.1021/jm00118a013

The isomeric (17α,20E)- and (17α,20Z)-(iodovinyl)estradiol derivatives 3 and 6, and their no-carrier-added (nca) [¹²⁵I]iodovinyl analogues, were tested for their relative target tissue retention and binding affinity for the estrogen receptor. The (iodovinyl)estradiols 3 and 6 were prepared via destannylation of the (17α,20E)- and (17α,20Z)-tributylstannyl precursors 2 and 4 with retention of configuration. Selective formation of the E or Z isomers 2 and 4 during the reaction of 17α-ethynylestradiol 1a with tri-n-butyltin hydride was controlled by the presence or absence of the catalyst, the polarity of the solvent, and the reaction temperature. The nca [¹²⁵I]iodovinyl analogues [¹²⁵I]-3a and [¹²⁵I]-6a were obtained in good radiochemical yield and high purity by treatment of 2a and 4a with [¹²⁵I]NaI in the presence of H₂O₂ and chloroamine-T, respectively. Of the two isomeric iodovinyl derivatives 3 and 6, the 20Z isomer 6a exhibited the highest receptor binding affinity and the [¹²⁵I]-6a gave the highest in vivo receptor-mediated target tissue uptake.