Processes for preparation of 9,11 epoxy steroids and intermediates useful therein

Abstract

Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone and other compounds of Formula I wherein: -A-A- represents the group —CHR 4 —CHR 5 — or —CR 4 ═CR 5 — —R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, aryloxy, R 1 represents an alpha-oriented lower alkoxycarbonyl or hydroxyalkyl radical, —B—B— represents the group —CHR 6 —CHR 7 — or an alpha- or beta-oriented group: where R 6 and R 7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, aryloxy, and R 8 and R 9 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, aryloxy, or R 8 and R 9 together comprise a carbocyclic or heterocyclic ring structure, or R 8 or R 9 together with R 6 or R 7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.

1 - 65 . (canceled)  
   
   
       66 . A compound of Formula VIII  
     
       
         
         
             
             
         
       
     
     wherein 
 -A-A- represents the group —CHR 4 —CHR 5 — or —CR 4 ═CR 5 — 
 R 3 , R 4  and R 5  are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, and aryloxy,  
 —B—B— represents the group —CHR 6 —CHR 7 — or an alpha- or beta-oriented group:  
                     
 where R 6  and R 7  are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, and aryloxy, and  
 R 8  and R 9  are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, and aryloxy, or R 8  and R 9  together comprise a carbocyclic or heterocyclic ring structure, or R 8  and R 9  together with R 6  or R 7  comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.  
 
   
   
       67 . A compound of Formula VIII as set forth in  claim 66  wherein said compound corresponds to Formula VIIIA:  
     
       
         
         
             
             
         
       
     
     wherein: 
 -A-A- represents the group —CH 2 —CH 2 — or —CH═CH—,  
 —B—B— represents the group —CH 2 —CH 2 — or an alpha- or beta-oriented group:  
                     
 X represents two hydrogen atoms or oxo,  
 Y 1  and Y 2  together represent the oxygen bridge —O—, or  
 Y 1  represents hydroxy, and  
 Y 2  represents hydroxy, lower alkoxy or, if X represents H 2 , also lower alkanoyloxy, and salts of compounds in which X represents oxo and Y 2  represents hydroxy.  
 
   
   
       68 . A compound of Formula VIII as set forth in  claim 66  wherein said compound is  
     
       
         
         
             
             
         
       
     
   
   
       69 . A compound according to  claim 66 , wherein said compound of Formula VIII is 11α,17α-Dihydroxy-3-oxopregna-4,6-diene-21-carboxylic Acid, γ-Lactone.  
   
   
       70 . A compound of Formula XIV:  
     
       
         
         
             
             
         
       
       wherein: 
 -A-A- represents the group —CHR 4 —CHR 5 — or —CR 4 ═CR 5 —,  
 R 3 , R 4  and R 5  are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, and aryloxy, and  
 —B—B— represents the group —CHR 6 —CHR 7 — or an alpha- or beta-oriented group:  
                     
 
       where R 6  and R 7  are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, and aryloxy.  
     
   
   
       71 . A compound of  claim 70  wherein: 
 R 3  is hydrogen,    -A-A- represents the group —CH 2 —CH 2 —, and    —B—B— represents the group —CH 2 —CH 2 —.    
   
   
       72 . A compound of  claim 70  having the structural formula:  
     
       
         
         
             
             
         
       
     
   
   
       73 . A compound corresponding to Formula 101:  
     
       
         
         
             
             
         
       
       wherein: 
 -A-A-  
 
       represents the group — 
       CHR 4 —CHR 5 — or —CR 4 ═CR 5 —, 
 R 3 , R 4  and R 5  are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, and aryloxy,  
 R 11  is C 1 -C 4  alkyl, and  
 —B—B— represents the group —CHR 6 —CHR 7 — or an alpha- or beta-oriented group:  
                     
 
       where R 6  and R 7  are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano, and aryloxy.  
     
   
   
       74 . A compound of  claim 73  wherein: 
 R 3  is selected from the group consisting of hydrogen, lower alkyl and lower alkoxy,    -A-A- represents the group —CH 2 —CH 2 —, and    —B—B— represents the group —CH 2 —CH 2 —.    
   
   
       75 . A compound of  claim 73  wherein R 3  is hydrogen.  
   
   
       76 . A compound of  claim 74  wherein R 11  is methyl.  
   
   
       77 . A compound of  claim 74  wherein R 11  is ethyl.