Numazawa M, Kimura K, Nagaoka M
Steroids. 1981 Nov;38(5):557-65. doi: 10.1016/0039-128x(81)90054-4.
A novel synthesis of sodium 17-oxo-16 alpha-hydroxy-1,3,5(10)-estratrien-3-yl sulfate (4), sodium 16 alpha, 16 beta-dihydroxy-1,3,5(10)-estratrien-3-yl sulfate (5) and sodium 16-oxo-17 beta-hydroxy-1,3,5(10)-estratrien-3-yl sulfate (6) is described. 16 alpha-Bromo-3-hydroxy-1,3,5(10)-estratrien-17-one (1) was efficiently synthesized in one step with 70-97% yield by bromination of 3-hydroxy-1,3,5(10)-estratrien-17-one with cupric bromide. 3,16 alpha-Dihydroxy-1,3,5(10)-estratrien-17-one (3) was quantitatively obtained by controlled stereospecific hydrolysis of the bromoketone 1 with sodium hydroxide in aqueous pyridine. The bromoketone 1 was converted to the 16 alpha-hydroxy-17-ketone 3-sulfate 4 by sulfation with chlorosulfonic acid in pyridine and a subsequent controlled hydrolysis in a high yield without formation of the other ketols. Treatment of the sulfate 4 with sodium borohydride have the triol sulfate 5. The sulfate 4 was also rearranged to the 17 beta-hydroxy-16-ketone 6 with sodium hydroxide in water in a quantitative yield.
描述了17-氧代-16α-羟基-1,3,5(10)-雌甾三烯-3-基硫酸酯钠（4）、16α,16β-二羟基-1,3,5(10)-雌甾三烯-3-基硫酸酯钠（5）和16-氧代-17β-羟基-1,3,5(10)-雌甾三烯-3-基硫酸酯钠（6）的一种新合成方法。16α-溴-3-羟基-1,3,5(10)-雌甾三烯-17-酮（1）通过用溴化铜对3-羟基-1,3,5(10)-雌甾三烯-17-酮进行溴化反应一步高效合成，产率为70 - 97%。3,16α-二羟基-1,3,5(10)-雌甾三烯-17-酮（3）通过在吡啶水溶液中用氢氧化钠对溴代酮1进行可控立体选择性水解定量得到。溴代酮1通过在吡啶中用氯磺酸硫酸化，随后进行可控水解，以高收率转化为16α-羟基-17-酮3-硫酸酯4，且不形成其他酮醇。用硼氢化钠处理硫酸酯4得到三醇硫酸酯5。硫酸酯4在水中用氢氧化钠重排为17β-羟基-16-酮6，产率定量。
