Stereochemical probes for the estrogen receptor: Synthesis and receptor binding of (17α,20E/Z)-21-phenyl-19-norpregna-1,3,5(10), 20-tetraene-3,17β-diols

摘要

Previous studies from our laboratory using 17α-E- and 17α-Z-halovinyl and phenylthiovinyl estradiols demonstrated a marked preference for the Z stereochemistry and a significant steric tolerance for the Z-vinyl substitu-ent. To further explore the extent of that Stereochemical preference and steric tolerance we have prepared stereoselectively the 17α-E- and 17α-Z-phenylvinyl estradiols (E- and Z-styrylestradiols). The results, in addition to demonstrating a facile preparation of the target compounds, supported the previously observed Stereochemical and steric effects. The relative binding affinities for the Z isomer were 3-4-fold greater than the E isomer at both 4℃ and 25℃, and only one-half to one-fourth those of estradiol under similar conditions. The developing model for ligand-accessible space within the estrogen receptor suggests that Z-phenylvinyl estradiols may provide interesting and useful probes for mapping the receptor.