This invention relates to the novel processes for the preparation of 9,11-epoxy steroid compounds, especially those of the 20-spiroxane series and their analogs, novel intermediates useful in the preparation of steroid compounds, and processes for the preparation of such novel intermediates. Most particularly, the invention is directed to novel and advantageous methods for the preparation of methyl hydrogen 9,11.alpha.-epoxy-17.alpha.-hydroxy-3-oxopregn-4-ene-7.alpha.,21-dicarboxy late, .gamma.-lactone (eplerenone; epoxymexrenone).
Methods for the preparation of 20-spiroxane series compounds are described in U.S. Pat. No. 4,559,332. The compounds produced in accordance with the process of the '332 patent have an open oxygen containing ring E of the general formula: ##STR2##
in which
--A--A-- represents the group --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, PA1 R.sup.1 represents an .alpha.-oriented lower alkoxycarbonyl or hydroxycarbonyl radical. PA1 --B--B-- represents the group --CH.sub.2 --CH.sub.2 -- or an .alpha.- or .beta.-oriented group ##STR3## PA1 R.sup.6 and R.sup.7 being hydrogen PA1 X represents two hydrogen atoms or oxo, PA1 Y.sup.1 and Y.sup.2 together represent the oxygen bridge --O--, or PA1 Y.sup.1 represents hydroxy, and PA1 Y.sup.2 represents hydroxy, lower alkoxy or, if X represents H.sub.2, also lower alkanoyloxy, PA1 and salts of such compounds in which X represents oxo and Y.sup.2 represents hydroxy, that is to say of corresponding 17.beta.-hydroxy-21-carboxylic acids. PA1 --A--A-- represents the group --CHR.sup.4 --CHR.sup.5 -- or --CR.sup.4.dbd.CR.sup.5 -- PA1 R.sup.3, R.sup.4 and R.sup.5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxy carbonyl, cyano, aryloxy, PA1 R.sup.1 represents an alpha-oriented lower alkoxycarbonyl or hydroxycarbonyl radical, PA1 R.sup.2 is an 11.alpha.- leaving group the abstraction of which is effective for generating a double bond between the 9- and 11- carbon atoms; PA1 --B--B-- represents the group --CHR.sup.6 --CHR.sup.7 -- or an alpha- or beta- oriented group: ##STR5## PA1 R.sup.8 and R.sup.9 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, aryloxy, or R.sup.8 and R.sup.9 together comprise a carbocyclic or heterocyclic ring structure, or R.sup.8 or R.sup.9 together with R.sup.6 or R.sup.7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.
U.S. Pat. No. 4,559,332 describes a number of methods for the preparation of epoxymexrenone and related compounds of Formula IA. The advent of new and expanded clinical uses for epoxymexrenone create a need for improved processes for the manufacture of this and other related steroids.
USPTO Backgrounds
USPTO Backgrounds