1. 研究目的与意义（文献综述包含参考文献）

1、醋酸乌利司他的简介 醋酸乌利司他（ulipristal acetate，1），化学名为17- 乙酰氧基 #8211;11- (4- 二甲胺基苯基) -19- 去甲孕甾 -4,9- 二烯 -3,20- 二酮，cas号为126784-99-4，分子量为433.5824。

是一种新型口服紧急避孕药，是美国目前市售的新一代紧急避孕药ella的活性化学成分。

它不仅能在妇女无保护性交后长达120h内用药，且紧急避孕效力不会随用药时间延迟而下降，同时安全性和耐受性均很好。

2. 研究的基本内容、问题解决措施及方案

1、 课题研究内容 现文献已经报道有多种合成方法来制备醋酸乌利司他，但是所得的产物的纯度不同，效率及难易程度也有很大差异，所以要找到一种兼顾收率、产物纯度以及安全性环保性的醋酸乌利司他合成途径。

通过前期的文献调研确定合成路线，并完成醋酸乌利司他合成工艺的打通及反应参数优化。

2、 课题研究方案 参考文献: [1] glasier a f, cameron s t, fine p m, et al. ulipristal acetate versus levonorgestrel for emergency contraception: arandomized non-inferiority trial and meta-analysis [j] . lancet, 2010, 375(9714): 555-562. [2] golsteyn rm. gefitinib does not increase survival in lung cancer patients [j]. drug discov today, 2005, 10(6): 381. [3] us fda. ella (ulipristal acetate) tablet's prescribing information [eb/ol].[2014-05-20]. [4] jones hk, stafford le, swaisland hc, et al. a sensitive assay for zd1839 (iressa) in human plasma by liquid-liquid extraction and high performance liquid chromatography with mass spectrometric detection: validation and use in phase i clinical trials [j]. j pharm biomed analysis, 2002, 29(1-2):221-228. [5] faivre l, gomo c, mir o, et al. a simple hplc-uv method for the simultaneous quantifi cation of gefi tinib and erlotinib in human plasma [j]. j chromatogr b analyt technol biomed life sci, 879(23): 2345-2350. [6] ( a) rao pn, acosta ck, bahr ml, et al. a practical large-scale synthesis of 17-acetoxy-11-( 4-n,ndimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (cdb-2914) [j]. steroids, 2000, 65(7): 395-400. (b)kim hk, blye rp, rao pn, et al. structural modification of 19-norprogesteroneⅠ: 17-alpha-substituted-11-betasubstituted-4-aryl and 21-substituted 19-norpregnadienedione as new antiprogestational agents: us, 20050143365 [p].2005-06-30. [7] 刘宏斌,高建永,韩广甸.醋酸乌利司他合成路线图解 [j].中国医药工业杂志,2011,42(1):73-75. [8] dancsi l, visky g,tuba z,et al.industrial process for the synthesis of 17-acetoxy-11-(4-n,n-dimetnylaminophenyl)-19-norpregna-4,9-diene-3,20-dione and new intermediates of the process: wo, 2007144674 [p]. 2007-12-21. [9] cook ce, wani mc, lee yw, et al. 11-substituted progesterone analogs: wo, 198912448 [p].1989-12-28. [10] chabber-buffet n, meduri g, bouchard p, et al selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications［j］human reproduct update, 2005, 11( 3) : 293-307． [11] hyun k kim, pemmaraju narasinha rao, james e burdett jr, et al, method for preparing 17a-acetoxy-11β-( 4-n, n-dimethylaminophyl ) -19-norpregna-4，9-diene-3, 20-dione, intermediates useful in the method, and methods for the preparation of such intermediates: us,5929262［p］.1999-07-27. [12] luis octavio silva guisasola, luis gerardo gutierrez fuentes, carlos roson nino, et al, method for obtaining 17α-acetoxy-11β-( 4-n,n-dimethylaminophyl ) -19-norpregna-4,9-diene-3,20-dione: us, 2006 /0247452［p］,2006-11-02. [13] 刘兆鹏,张灿飞,周义刚.醋酸乌利司他关键中间体的制备方法:中国, 103073612 [p].2013-05-01. [14] lane bs, vogt m, derose vj, et al. manganese-catalyzed epoxidations of alkenes in bicarbonate solutions [j]. j am chem soc, 2002, 124(40): 11946-11954. [15] murray rw, singh m, jeyaraman r. dioxiranes. 20. preparation and properties of some new dioxiranes [j]. j am chem soc, 1992, 114: 1346-1351. [16] syamala ms, jagattaran d, sundarababuy b, et al. a novel and highly β-selective epoxidation of △ 5-unsaturated steroids with permanganate ion [j]. j org chem, 1992, 57:1928-1930. [17] (a) 李 航,何党军.一种合成孕酮受体调节剂优利司特的合成方法:中国,102372760 [p]. 2012-03-14. (b) dancsi l, visky g, tuba z, et al. industrial process for the synthesis of 17alpha-acetoxy-11beta-[4-(n,n-dimethyl-amino)-phenyl]- 19-norpregna-4,9-diene-3,20-dione and new intermediates of the process: us, 2009187032 [p]. 2009-07-23.