Synthetic Research Of Aldosterone Receptor Antagonist Eplerenone

Eplerenone, a first selective andosterone blocker,is an orally-active aldosterone antagonist developed by Searle(Pharmacia) for the treatment of hypertension and congestive heart failure (CHF).Comparing to the non-selective andosterone blocker of Spironolactone,it has less site effects.The paper is a study about the synthesis of Eplerenone.Based on the analysis of the synthesis described in the reference,we firstly prepare 4,9(11)-androstaiene-3,17-dione by two methods,whicn is priority is that though 3 steps reactions including of oxidation,tosylation and elimination from 11-epi-hydrocortisone as the starting material And then we prepare Δ⁹⁽¹¹⁾Canrenone from 4,9(11)-androstaiene-3,17- dione though 5 Steps reaction with Trimethyl orthobutyrate,S-yilde, Diethyl phosphite,DMF-NaCl,and Chloranil. The total yield of the 8 steps is 34.3%.From Δ⁹⁽¹¹⁾ Canrenone, we make it react with diethylaluminum cyanide(Et₂AlCN),DIBAL-H, Jones' regent, Diazomethane and H₂O₂,the yield is 37.9%.Considering some dangerous regents are used in the methed, it maybe has some localization of its industrialization.So we try to design another route to prepare Eplerenone from Δ⁹⁽¹¹⁾ Canrenone.Although we get Eplerenone by another method from Δ⁹⁽¹¹⁾ Canrenone, reacting with Acetone cyanohydrin,and then with 1NHCl,25% Sodium methoxide and H₂O₂, the yield is poor.Eplerenone has been confirmed by element analys ,MS,NMR ,and they are all in accord with the reference.The purity of Eplerenone is 99.6% analysed by HPLC.