依普利酮的合成路线及参考文献？ ¹

依普利酮是一种高血压药物，属于高选择性醛酮受体拮抗剂。它通过竞争性抑制醛固酮与盐皮质激素受体结合，从而降低血压。

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 useful therein. US 6180780

参考文献：

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

合成路线3

参考文献：

Wuts PGML 2004. Processes for preparing 7-carboxy substituted steroids. US 2004087562

合成路线4

参考文献：

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

合成路线5

依普利酮合成的主要难点在于引入carbomethoxy取代基。下面是由Pharmacia&Upjohn制药厂开发的合成路线，通过furylation引入carbomethoxy取代基。

参考文献：

Wuts PGM 2004. Processes for preparing C-7 substituted steroids. US 2004097475

合成路线6

参考文献

Pearloan BA, Padilla AG, et al. 2006. A new approach 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 intermediates. WO 9825948

Ng JS, Wang PT, et al. 1997. Preparation of 7-carboxyl-9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olefinic double bonds. WO 9721720

Wang S, Li J, et al. 2006. Synthesis of eplerenone from 11β-hydroxycanrenone. 发明专利申请公开说明书, CN 1749266

Wiecrorek JJ, Maisto KD, et al. 2005. An improved process for the preparation of 9,11-epoxy steroids. WO 2005092913

Ye W, Lu C, et al. 2006. Preparation of methyl 9α,11α-epoxy-17β-hydroxy 3-oxo-pregn-4-ene-7,21-di-carboxylate electone (eplerenone). 发明专利中请公开说明书, CN 1724557

来源：博普智库