Hanson R N, Herman L W, Fiaschi R, Napolitano E
Department of Pharmaceutical Sciences, Bouve College of Pharmacy and Health Sciences, Northeastern University, Boston 02115, USA.
Steroids. 1996 Dec;61(12):718-22. doi: 10.1016/s0039-128x(96)00201-2.
Previous studies from our laboratory using 17 alpha-E- and 17 alpha-Z-halovinyl and phenylthiovinyl estradiols demonstrated a marked preference for the Z stereochemistry and a significant steric tolerance for the Z-vinyl substituent. To further explore the extent of that stereochemical preference and steric tolerance we have prepared stereoselectively the 17 alpha-E- and 17 alpha-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 degrees C and 25 degrees C, 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.
我们实验室之前使用17α-E-和17α-Z-卤代乙烯基及苯硫基乙烯基雌二醇进行的研究表明，对Z立体化学有明显偏好，对Z-乙烯基取代基有显著的空间耐受性。为了进一步探究这种立体化学偏好和空间耐受性的程度，我们立体选择性地制备了17α-E-和17α-Z-苯乙烯基雌二醇（E-和Z-苯乙烯基雌二醇）。结果除了表明目标化合物易于制备外，还支持了之前观察到的立体化学和空间效应。在4℃和25℃下，Z异构体的相对结合亲和力比E异构体大3至4倍，在类似条件下仅为雌二醇的二分之一至四分之一。雌激素受体内配体可及空间的发展模型表明，Z-苯乙烯基雌二醇可能为绘制受体图谱提供有趣且有用的探针。
