依普利酮是一种抗高血压药物, 属于高选择性醛酮受体拮抗剂。其作用机制为通过竟争性方式抑制醛固酮与盐皮质激素受体结合, 并拮抗醛固酮与盐上质激素受体结合而发挥其降低血压的作用。
合成路线1
参考文献:
Ng JS,Wang PT,et al.2001.Processes for preparation of 9,11-epoxy steroids and intermediates usefultherein. US 6180780
参考文献:
Ng JS.,Wang PT.et dl 2001.Proceoes for preparation of s,11-epoxy steroids aod internediates usefudlthereinUS 6180780
合成路线2
参考文献:
Ng JS,Wang PT,et al. 2001.Processes for preparation of 9,11-epoxy steroids and intermediates usefultherein. US 6180780
合成路线3
参考文献:
Wuts PGML 2004. Processes for preparing 7-carboxy substituted steroida. US2004087562
合成路线4
参考文献:
Wuts PGM 2004.Processes for preparing 7-carboxy subetituted steroids.US 2004087562
合成路线5
依普利酮合成的主要难点在于引人 carbomethoxy取代基，下面是由 Pharmacia&Upjohn制药厂开发的合成路线,通过furylation引人 carbomethoxy 取代基。
参考文献:
Wuts PGM 2004.Proccsses for preparing C-7 subetituted steroid.US 2004097475
合成路线6
参考文献
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
其他有关依普利酮合成的文献:
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. 发明专利申请公开说明书,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). 发明专利中请公开说明书, CN 1724557
来源：博普智库