The Synthesis Of New Drugs Drospirenone Intermediates Aemce In

3 β-acetoxyl-17,17-ethylendioxy-15β, 16β-methylene-7a-chloro-6β-epoxandrostane (AEMCE) is a kind of very important intermediate of the new sythetic medicine drospirenone. Drospirenone is different of the corpus luteum hormone of oral contraceptive, it is the derivative of the diuretic spironolactone, and it is a novel highly active mineralocorticoid antagonist. Drospirenone is combined with ethinylestradiol to afford a new contraceptive Yasrnin.In this paper, the synthetic technologies o f this intermediate were described and evaluated. The synthetic route and the experimental plans were put forward, and their reaction mechanism and preparing technologies were studied systematically. Moreover, the synthetic technologies of every step Were optimized.The intermediate was prepared from 3 β-acetoxyl-15 β, 16β -methyle-5-en-androst-17-one by protection, oxidation, reduction, epoxidation and chloridization. The influences of the molar ratio of reactants, the amount of catalyst, the time and temperature of reaction on the reaction results were studied, and the opotimum technological conditions for the protection were obtained by orthogonal experiments. The protection reaction is stability, the yield could reach 93.0%. The best reaction technology was obtained by contrasted the different oxidant, the molar ratio of reactants, the temperature and addition's mode . The optimum technological conditions for the oxidation were as following: the oxidant chromium trioxide-pyridine(l:2), the molar ratio of reactants 12:1, temperature 30℃, the yield was 70.5%. The influences of types of reducers, the molar ratio of reactants, the time and temperature of reaction on the reduction reaction were studied, and the optimum chnological conditions were obtained. The experimental results showed that the chemoselectivity and stereoselectivity of lithium tri-t-butoxyalumimium hydride were better than that of sodium horohydride, the yield was 77.5%. The 5β, 6β-epoxide was synthesized with t-butyl hydroperoxide as epoxidizing agent and vanadium acetylacetonate as catalyst. The optimum conditions were as following: the molar ration of reactants2.35:1, reaction temperature 60 reaction time 3 h, and the amount of catalyst 0.017:1, the yield was 76.9%. 7a- chlorizate was synthesized with triphenylphos phine carbon tetrachloride as chlorizating agent and pyridine as catalyst and heated under refux. The influences of the molar ratio of reactants, the amount of catalyst, the amount of solvent and the time on the chlorization were studied, and the optimum conditions were obtained by orthyogonal experiments. The yield was 62.0%. The overall yield was 24.2%. The products were confirmed by IR, TLC and melting point.