Method for preparing substituted 3,7-dihydroxy steroids

Abstract

The invention relates to a 17α-alkynyl-androst-5-ene-3β,7β,17β-triol compound essentially free of steroid side-product lacking an oxygen substituent at position 7 and processes for preparing the same.

What is claimed is: 
     
         1 . A 17α-alkynyl-androst-5-ene-3β,7β,17β-triol compound essentially free of steroid side-product lacking an oxygen substituent at position 7, made by a process comprising the steps of,
 (a) contacting a compound having the structure 
 
       
         
           
           
               
               
           
         
         with a reducing agent to convert the ═O functional group at position 7 to hydroxy predominantly in the β-configuration, wherein R 1  is —H, C 1-6  alkyl, C 3-6  cycloalkyl, optionally substituted aryl or optionally substituted heteroaryl and R 2  is —H, C 1-6  alkyl or aryl; 
         (b) converting the ═NOR 2  group at position 17 in the reaction product from step (a) to a ═O group to obtain a 7β-hydroxy-17-one compound; 
         (c) converting the —OC(O)R 1  group at position 3 of the 7β-hydroxy-17-one compound to a 3β-hydroxy derivative of the 7β-hydroxy-17-one; 
         (d) converting the hydroxy groups at positions 3 and 7 in the 3β-hydroxy derivative of the 7β-hydroxy-17-one compound from step (c) to (R 3 ) 3 SiO— groups, wherein each R 3  independently is C 1-6  alkyl or aryl; and 
         (e) contacting the reaction product of step (d) with an compound having the structure of M-C═C—Si(R 5 ) 3 , wherein R 5  independently are C 1-6  alkyl or aryl and M is a Group I, Group II or transition metal, wherein 17α-alkynyl-androst-5-ene-3β,7β,17β-triol essentially free of 17α-alkynyl-androst-5-ene-3β,17β-diol is obtained. 
       
     
     
         2 . The compound of  claim 1 , wherein R 1  is C 1-6  alkyl or phenyl. 
     
     
         3 . The compound of  claim 2 , wherein R 1  is —CH 3 . 
     
     
         4 . The compound of  claim 2 , wherein R 1  and R 2  are —CH 3 . 
     
     
         5 . The compound of  claim 1 , wherein M is Li, Mg or Zn. 
     
     
         6 . The compound of  claim 1 , wherein R 5  is —CH 3 . 
     
     
         7 . The compound of  claim 1 , wherein M is Li and R 5  is —CH 3 . 
     
     
         8 . The compound of  claim 1 , comprising the additional step of purifying the 7α-alkynyl-androst-5-ene-3β, 7β, 17β-triol compound of step (f) by recrystalization. 
     
     
         9 . The compound of  claim 8 , wherein R 1  is —CH 3 . 
     
     
         10 . The compound of  claim 8 , wherein R 1  and R 2  are —CH 3 . 
     
     
         11 . The compound of  claim 8 , wherein M is Li, Mg or Zn. 
     
     
         12 . The compound of  claim 8 , wherein R 5  is —CH 3 . 
     
     
         13 . The compound of  claim 8 , wherein M is Li and R 5  is —CH 3 . 
     
     
         14 . The compound of  claim 8 , wherein the 17α-alkynyl-androst-5-ene-3β,7β,17β-triol compound of step (f) is purified by recrystallization from methanol-water. 
     
     
         15 . The compound of  claim 14 , wherein R 1  is —CH 3 . 
     
     
         16 . The compound of  claim 14 , wherein M is Li, Mg or Zn. 
     
     
         17 . The compound of  claim 14 , wherein R 5  is —CH 3 . 
     
     
         18 . The compound of  claim 1 , wherein the 17α-alkynyl-androst-5-ene-3β,7β,17β-triol compound is 17α-ethynyl-androst-5-ene-3β,7β,17β-triol. 
     
     
         19 . The compound of  claim 8  wherein the 17α-alkynyl-androst-5-ene-3β,7β,17β-triol compound is 17α-ethynyl-androst-5-ene-3β,7β,17β-triol. 
     
     
         20 . The compound of  claim 14 , wherein the 17α-alkynyl-androst-5-ene-3β,7β,17β-triol compound is 17α-ethynyl-androst-5-ene-3β,7β,17β-triol.