Oda T, Sakakibara Y, Sato Y, Hanzawa H, Hata T
Kyoritsu College of Pharmacy, Shibakoen 1-chome, Minato-ku, Tokyo, Japan.
Chem Pharm Bull (Tokyo). 1992 Mar;40(3):588-92. doi: 10.1248/cpb.40.588.
Indenestrol A (IA) is a metabolite of diethylstilbestrol (DES), and indenestrol B (IB) is an analog of IA. IA was simply obtained from E,E-dienestrol in the presence of dilute sulfuric acid, and a mixture of IA and IB was formed by thermal cyclization of E,E-dienestrol. In order to elucidate the effects of optically active IA and IB on microtubule assembly, the IA and IB enantiomers were separated to greater than 99% purity by high-pressure liquid chromatography using a chiral column. The di(4-bromobenzoate) of (-)-IB was analyzed by X-ray crystallography and its absolute structure was determined as C(3)-S. The (+)-, (-)-, and (+/-)-indenestrols A and B were shown to be inhibitors of microtubule assembly in vitro using microtubule proteins from porcine brain. (+/-)-IB is more active than (+/-)-IA, and the order of inhibitory activity of the enantiomers on microtubule assembly was (+)-IB greater than (+)-IA greater than (-)-IA greater than (-)-IB.
茚雌酚A（IA）是己烯雌酚（DES）的一种代谢产物，茚雌酚B（IB）是IA的类似物。IA可在稀硫酸存在的情况下简单地由E，E-二烯雌酚制得，并且IA和IB的混合物通过E，E-二烯雌酚的热环化反应形成。为了阐明旋光性IA和IB对微管组装的影响，使用手性柱通过高压液相色谱法将IA和IB对映体分离至纯度大于99%。通过X射线晶体学分析了（-）-IB的二（4-溴苯甲酸酯），并确定其绝对结构为C（3）-S。使用来自猪脑的微管蛋白，（+）-、（-）-和（+/-）-茚雌酚A和B在体外被证明是微管组装的抑制剂。（+/-）-IB比（+/-）-IA更具活性，并且对映体对微管组装的抑制活性顺序为（+）-IB大于（+）-IA大于（-）-IA大于（-）-IB。
