107724-20-9 / 依普利酮的合成路線

依普利酮是一種抗高血壓藥物, 屬于高選擇性醛酮受體拮抗劑。其作用機制為通過竟爭性方式抑制醛固酮與鹽皮質激素受體結合, 并拮抗醛固酮與鹽上質激素受體結合而發(fā)揮其降低血壓的作用。

合成路線1

參考文獻:

Ng JS,Wang PT,et al.2001.Processes for preparation of 9,11-epoxy steroids and intermediates usefultherein. US 6180780

參考文獻:

Ng JS.,Wang PT.et dl 2001.Proceoes for preparation of s,11-epoxy steroids aod internediates usefudlthereinUS 6180780

合成路線2

參考文獻:

Ng JS,Wang PT,et al. 2001.Processes for preparation of 9,11-epoxy steroids and intermediates usefultherein. US 6180780

合成路線3

參考文獻:

Wuts PGML 2004. Processes for preparing 7-carboxy substituted steroida. US2004087562

合成路線4

參考文獻:

Wuts PGM 2004.Processes for preparing 7-carboxy subetituted steroids.US 2004087562

合成路線5

依普利酮合成的主要難點在于引人 carbomethoxy取代基，下面是由 Pharmacia&Upjohn制藥廠開發(fā)的合成路線,通過furylation引人 carbomethoxy 取代基。

參考文獻:

Wuts PGM 2004.Proccsses for preparing C-7 subetituted steroid.US 2004097475

合成路線6

參考文獻

Pearloan BA,Padilla AG,et al 2006. A new approech to the furan degradation problem involving oconoly-sis of the trans enediope and its use in& cost-effective synthesis of eplerenone Org Lett, 8: 2111~2113

其他有關依普利酮合成的文獻:

Ng JS,Liu C,et al. 1998. Processes for preparation of 9,11-epoxy steroids and their intertnediates.WO 9825948Ng JS,Wang PT,et al.1997. Preparation of 7ecarboxyl-9,11-epoxy steroids and intermoediates usefultherein and a general process for the epoxidation of olefinic double bonds."WO 9721720

Wang S,Li J,et al. 2006. Synthesis of eplerenone from 1lar-hydroxycanrenone. 發(fā)明專利申請公開說明書,CN 1749266Wiecrorek JJ,Maisto KD,et al. 2005.An improved process for the preparation of 9,11-epoxy steroidsWO 2005092913

YeW,Lu C,et al 2006.Preparation of methyl 9a,1larepoxy-179-hydroxy 3-oxo-pregn-4-ene7,21-di-carboxylate rlectone (eplerenone). 發(fā)明專利中請公開說明書, CN 1724557

來源：博普智庫