6β,7β;15β,16β-Dimethylene-17β-Dihydroxy-17α-(2-Carbonyl)-Ethyl-Androst-4-En-3-One置于对甲苯磺酸体系中,用 乙酸乙酯 作为反应溶剂,化学反应 1.0H,反应生成 屈螺酮 参考文献: Process For Obtaining 17-Spirolactones In Steroids[fr] Procédé D'Obtention De 17-Spirolactones Dans Des Stéroïdes 标题: Process For Obtaining 17-Spirolactones In Steroids[fr] Procédé D'Obtention De 17-Spirolactones Dans Des Stéroïdes 摘要:该发明涉及获取17位上具有螺内酯基团的类固醇的过程,特别是工业上获取6β,7β; 15β,16β-二甲烯-3-酮-17α-孕-4-烯-21,17-碳内酯,通常称为drospirenone,以及在该过程中有用的中间体.
专利号:US-8841283-B2 优先权日:2010-08-03 标 题 :Methods for the preparation of drospirenone and intermediates thereof 发明人:MONTORSI MAURO; MARIANI EDOARDO; GAMBARIN LUCA; ORRU′ GIANMAURO; SCALAPRICE ROMEO; MERLO MASSIMO; ANDRIOLO ERIKA 权利人:MONTORSI MAURO; MARIANI EDOARDO; GAMBARIN LUCA; ORRU′ GIANMAURO; SCALAPRICE ROMEO; MERLO MASSIMO; ANDRIOLO ERIKA; NEWCHEM S P A 摘要:The invention relates to a process for the preparation of Drospirenone in high yields and purity starting from a compound of formula 2 n n n n n n n n n n n n wherein R is a hydroxyl protective group as defined in the claims, through a sequence of oxidation, deprotection, lactonization and water elimination steps, and wherein the steps of oxidation and lactonization are performed with 1,3,5-trichloro1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (trichloroisocyanuric acid, TCCA) or 1,3-dichloro-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione (dichloroisocyanuric acid, DCCA) or an alkaline metal salt thereof such as the sodium salt dihydrate (DCCA sodium salt) or 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (IBX). New synthetic intermediates useful for the synthesis of Drospirenone are disclosed, too.
专利号:WO-2014174338-A1 优先权日:2013-04-22 标 题:Process for preparing an intermediate useful in the production of drospirenone 发明人:LENNA ROBERTO; BARBIERI FRANCESCO; LUONI MARIA GIOVANNA; NOSEDA MONICA 权利人:IND CHIMICA SRL 摘要:A process is described wherein, using 17α-(3-hydroxyprapyl)-6β,7β,15β,16β- dimethylene-5β-androstane-3β,5,17β-triol (III) as starting product, there is obtained 3β,5-dihydroxy-6β,7β,15β,16β-dimethylene-5β-17α-pregna-21, 17-carbolactone (I), a useful intermediate in the synthesis of the compound drospirenone, having contraceptive action: (Formula III & I) (III) (I)
1: Borgo MV, Claudio ER, Silva FB, Romero WG, Gouvea SA, Moysés MR, Santos RL, Almeida SA, Podratz PL, Graceli JB, Abreu GR. Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats. Braz J Med Biol Res. 2016;49(1). pii: S0100-879X2016000100601. doi: 10.1590/1414-431X20154655. Epub 2016 Nov 17. 2: Wang Q, Ma X, He J, Sun Q, Li Y, Li H. Binding properties of drospirenone with human serum albumin and lysozyme in vitro. Spectrochim Acta A Mol Biomol Spectrosc. 2016 Jan 15;153:612-8. doi: 10.1016/j.saa.2015.09.017. Epub 2015 Sep 30. doi: 10.1111/bcp.12745. Epub 2015 Oct 28. doi: 10.1097/MBP.0000000000000139. doi: 10.3109/09513590.2015.1062860. Epub 2015 Jul 14. doi: 10.1016/j.contraception.2015.07.014. Epub 2015 Jul 29. doi: 10.1111/jth.13109. Epub 2015 Sep 14. doi: 10.1111/jog.12774. Epub 2015 Aug 26. doi: 10.1016/j.steroids.2015.07.008. Epub 2015 Jul 26. doi: 10.5468/ogs.2015.58.5.397. Epub 2015 Sep 22. 14: Al-Jefout M, Nawaiseh N. Continuous Norethisterone Acetate versus Cyclical Drospirenone 3 mg/Ethinyl Estradiol 20 μg for the Management of Primary Dysmenorrhea in Young Adult Women. J Pediatr Adolesc Gynecol. 2015 Sep 3. pii: S1083-3188(15)00310-1. doi: 10.1016/j.jpag.2015.08.009. [Epub ahead of print] doi: 10.12659/MSM.894926.
合成参考文献
参考文献:10.1055/s-0028-1087226 摘要:Bandini M, Umani-Ronchi A, Contento M, Garelli A, Monari M, Tolomelli A, Andriolo E, Montorsi M. A Nonclassical Stereoselective Semi-Synthesis of Drospirenone via Cross-Metathesis Reaction. Synthesis. 2008 Nov 06;2008(23):3801–4. doi: 10.1055/s-0028-1087226.