Kanojia R M, Allen G O, Killinger J M, McGuire J L
J Med Chem. 1979 Dec;22(12):1538-41. doi: 10.1021/jm00198a021.
The synthesis of 17-epi-ethynylestradiol (10), the 17 beta-ethynyl-17 alpha-ol epimer of the well-known orally active estrogen, ethynylestradiol (1), was achieved by LiA1H4 reduction of epoxide 9, as well as by demethylating epimestranol (11) with CH3MgI. Compound 11 was obtained by the unusual 17 beta-ethynylation of estrone 3-methyl ether 22 under equilibrating conditions. The in vitro estrogen receptor-binding affinity and the oral estrogenicity in the rat for the 17-epi compounds 10, 11 and 20 (epiquinestrol) was evaluated. Despite moderate estrogen receptor-binding affinity, compound 10 was devoid of measurable estrogenicity at 10 mg/kg or antiestrogenicity at 3 mg/kg.
17-表乙炔雌二醇（10）是著名的口服活性雌激素乙炔雌二醇（1）的17β-乙炔基-17α-醇差向异构体，它的合成可通过用LiAlH4还原环氧化物9以及用CH3MgI使表美雌醇（11）脱甲基来实现。化合物11是通过在平衡条件下对雌酮3-甲醚22进行不寻常的17β-乙炔基化反应得到的。评估了17-表化合物10、11和20（表喹雌醇）在体外与雌激素受体结合的亲和力以及在大鼠体内的口服雌激素活性。尽管化合物10与雌激素受体结合的亲和力中等，但在10mg/kg时没有可测量的雌激素活性，在3mg/kg时也没有抗雌激素活性。
