11α-羟基炔雌醚和11α-甲氧基炔雌醚的合成及其抗生育作用

为了寻找抗生育药物,从△⁹⁽¹¹⁾-雌素酮开始,经环戊醚化、缩酮化、硼氢化-氧化、甲基化、脱缩酮、乙炔化等反应合成了11α-羟基炔雌醚、11α-甲氧基炔雌醚。目的化合物及相应中间体的结构依据波谱分析等确定。小鼠实验表明这两个化合物不具明显抗生育活性。

Studies on the synthesis of 11 alpha-hydroxy-quinestrol, 11 alpha-methoxy-quinestrol and their antifertility activity

Quinestrol was used as the lead compound for studies on the new steroidal contraceptives for early pregnancy. The 11 α-hydroxyl and 11 α-methoxyl derivatives of quinestrol were synthesized. △⁹⁽¹¹⁾-Estrone was treated with cyclopentyl bromide and potassium carbonate to form the cyclopentyl ether (2). Hydroboration—oxidation of the ethylene ketal of (2) with B₂H₆—H₂O₂ and chromatographic separation on silica gel gave 11 α-hydroxide (4) and small amount of 11 β-hydroxide and compound (3). (4) was methylated with NaH/DMSO and methyl iodide to afford (5), The 11 α-methoxy-quinestrol (7) was obtained when. (5) was hydro- lized with 5% hydrochloric acid and then ethynylated with ethynyl lithium. While the 11 α-hydroxy-quinestrol (9) was obtained when (4)was treated with 10% hydrochloric acid and then ethynylated with ethynyl lithium. The configurations of the target compounds and their respective intermediates were confirmed by IR, MS, ¹HNMR and elemental analysis. Preliminary pharmacological result on mice showed that 11 α-hydroxy and 11 α-methoxy derivatives of quinestrol did not possess significant antifertility activity.