专利号:EP-1641812-B1 优先权日:2003-06-30 标题 :PURE d-(17alpha)-13-ETHYL-17-HYDROXY-18,19-DINORPREGN-4-ENE-20-YNE-3-ONE-3E- AND -3Z-OXIME ISOMERS, AS WELL AS PROCESS FOR THE SYNTHESIS OF THE MIXTURE OF ISOMERS AND THE PURE ISOMERS 发明人:TUBA ZOLTAN; MAHO SANDOR; KESERU GYOERGY; KOZMA JOZSEF; HORVATH JANOS; BALOGH GABOR 权利人:RICHTER GEDEON NYRT 摘要:The invention relates to the pure d-(17alpha)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-Â20-yne-3-one-3E-oxime isomer of formula (IA), the pure d-(17alpha)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yne-3-one-3Z-oxime isomer of formula (IB), which are of gestagen activity, as well as the process for the synthesis of the mixture of the above isomers and the pure isomers. The invention also relates to the pharmaceutical compositions - and the process for their synthesis - which contain either the pure isomer of formula (IA) or the pure isomer of formula (IB) as active ingredient as such or in combination with other active ingredients (for example an oestrogen agent) together with pharmaceutical auxiliary materials commonly used in practice.
专利号:US-7816546-B2 优先权日:2003-06-30 标 题:Process for the synthesis of high purity d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yn-3-one-oxime 发明人:TUBA ZOLTAN; MAHO SANDOR; KISS JANOS; MAGYARI ENDRENE; TERDY LASZLO 权利人:RICHTER GEDEON VEGYESZET 摘要:The invention relates to a process for the synthesis of d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yn-3-one-oxime (also known as norelgestromin) via acetylation of d-norgestrel at position 17; oximation of the oxo group at position 3 of the obtained d-(17α)-13-ethyl-17-(acetyloxy)-18,19-dinorpregn-4-ene-20-yn-3-one; and then hydrolyzing the acetyloxy group at position 17 of the obtained d-(17α)-13-ethyl-17-(acetyloxy)-18,19-dinorpregn-4-ene-20-yn-3-oxime derivative, thereby obtaining norelgestromin.
专利号:US-4045452-A 优先权日:1974-03-13 标题 :Steroid total synthesis process utilizing a cyanoalkyl A-ring precursor 发明人:COHEN NOAL; ROSENBERGER MICHAEL; SAUCY GABRIEL 权利人:HOFFMANN LA ROCHE 摘要:A multi-step, stereospecific total synthesis of steroids utilizing intermediates having a cyanoalkyl A-ring precursor is disclosed. The initial starting materials for this process are the relatively inexpensive and commercially available reagents γ-butyrolactone and sodium cyanide. The process is suitable for the preparation of racemic or optically active, medicinally valuable steroids, particularly 19-norsteroids. It is a feature of this process that conditions employed during the multiple step synthesis are selected so as to retain the normally labile nitrile group even during hydrogenation and hydrolysis steps. In this manner, it is possible to employ the nitrile group as an A-ring precursor without resorting to protective groups as wasl heretofore found necessary in previous steroid total synthesis processes.
专利号:US-4105676-A 优先权日:1975-12-22 标题 :Steroid total synthesis process utilizing a cyanoalkyl a-ring precursor 发明人:COHEN NOAL; ROSENBERGER MICHAEL; SAUCY GABRIEL 权利人:HOFFMANN LA ROCHE 摘要:A multi-step, stereospecific total synthesis of steroids utilizing intermediates having a cyanoalkyl A-ring precursor is disclosed. The initial starting materials for this process are the relatively inexpensive and commercially available reagents γ-butyrolactone and sodium cyanide. The process is suitable for the preparation of racemic or optically active, medicinally valuable steroids, particularly 19-norsteroids. It is a feature of this process that conditions employed during the multiple step synthesis are selected so as to retain the normally labile nitrile group even during hydrogenation and hydrolysis steps. In this manner, it is possible to employ the nitrile group as an A-ring precursor without resorting to protective groups as was heretofore found necessary in previous steroid total synthesis processes.
专利号:US-3965138-A 优先权日:1974-03-13 标 题:Steroid total synthesis process utilizing a cyanoalkyl A-ring precursor 发明人:COHEN NOAL; ROSENBERGER MICHAEL; SAUCY GABRIEL 权利人:HOFFMANN LA ROCHE 摘要:A multi-step, stereospecific total synthesis of steroids utilizing intermediates having a cyanoalkyl A-ring precursor is disclosed. The initial starting materials for this process are the relatively inexpensive and commercially available reagents γ-butyrolactone and sodium cyanide. The process is suitable for the preparation of racemic or optically active, medicinally valuable steroids, particularly 19-norsteroids. It is a feature of this process that conditions employed during the multiple step synthesis are selected so as to retain the normally labile nitrile group even during hydrogenation and hydrolysis steps. In this manner, it is possible to employ the nitrile group as an A-ring precursor without resorting to protective groups as was heretofore found necessary in previous steroid total synthesis processes.
专利号:US-3991084-A 优先权日:1970-08-26 标题 :Steroid total synthesis process utilizing a cyanoalkyl A-ring precursor 发明人:COHEN NOAL; ROSENBERGER MICHAEL; SAUCY GABRIEL 权利人:HOFFMANN LA ROCHE 摘要:A multi-step, stereospecific total synthesis of steroids utilizing intermediates having a cyanoalkyl A-ring precursor is disclosed. The initial starting materials for this process are the relatively inexpensive and commercially available reagents γ-butyrolactone and sodium cyanide. The process is suitable for the preparation of racemic or optically active, medicinally valuable steroids, particularly 19-norsteroids. It is a feature of this process that conditions employed during the multiple step synthesis are selected so as to retain the normally labile nitrile group even during hydrogenation and hydrolysis steps. In this manner, it is possible to employ the nitrile group as an A-ring precursor without resorting to protective groups as was heretofore found necessary in previous steroid total synthesis processes.
1: Bifano M, Sevinsky H, Hwang C, Kandoussi H, Jiang H, Grasela D, Bertz R. Effect of the coadministration of daclatasvir on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate. Antivir Ther. 2014;19(5):511-9. doi: 10.3851/IMP2718. Epub 2013 Dec 17. e1-8. doi: 10.1016/j.ajog.2014.09.014. Epub 2014 Sep 16. doi: 10.1136/bmj.f341. doi: 10.1177/1933719114526472. Epub 2014 Mar 19. doi: 10.1016/j.annder.2010.12.011. Epub 2011 Jan 22. French. doi: 10.1177/1060028015580637. Epub 2015 Apr 10. 18: Borsos A, Lampé L. [Contraception with d-norgestrel]. Orv Hetil. 1980 Jun 22;121(25):1495-8. Hungarian.
合成参考文献
摘要:US Natl Inst Health; DailyMed. Current Medication Information Low-ogestrel (Norgestrel and Ethinyl Estradiol) (March 2007). Available from, as of March 29, 2010: 摘要:Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990) 摘要:Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2747 摘要:Franke C et al; Chemosphere 29: 1501-14 (1994) 摘要:Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyclo-Progynova (Last updated March 2011). Available from, as of March 25, 2011: https://www.medicines.org.uk/EMC/medicine/9159/SPC/Cyclo-Progynova+2mg/