Practical, cost-effective synthesis of CoQ10

Abstract

The present invention provides a convergent method for the synthesis of ubiquinones and ubiquinone analogues. Also provided are precursors of ubiquinones and their analogues that are useful in the methods of the invention.

1 - 61 . (canceled)  
     
     
         62 . A compound of formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1 , R 2  and R 3  are independently selected C 1 -C 6  alkyl groups;  
 R 4  is H or a protecting group which, together with the phenol oxygen to which it is attached is a member selected from silyl ether, ester, carbonate and phosphinate;  
 R 5  is a member selected from the group consisting of branched, unsaturated alkyl, and —CH 2 Y, in which Y is OR 6 , SR 6 , NR 6 R 7 , or a leaving group;  
 R 6  and R 7  are members independently selected from H and branched, unsaturated alkyl.  
 
     
     
         63 . The compound according to  claim 62 , wherein Y is halogen.  
     
     
         64 . The compound according to  claim 62 , wherein each of R 1 , R 2  and R 3  is methyl.  
     
     
         65 . The compound according to  claim 62 , wherein at least one of R 5 , R 6  and R 7  has the formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 n is a member selected from the integers from 0 to 13.  
 
     
     
         66 . The compound according to  claim 65  wherein n is a member selected from the integers from 3 to 9.  
     
     
         67 . A compound having a structure of formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2  and R 3  are independently selected C 1 -C 6  alkyl groups; and  
 n is an integer from 0 to 13.  
 
     
     
         68 . A method for preparing a compound of formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1 , R 2  and R 3  are members independently selected from the group consisting of C 1 -C 6  alkyl groups;  
 n is a member selected from group consisting of the integers from 0 to 13, said method comprising:  
 (a) contacting a compound of formula:  
                     
 wherein,  
 R 10 , R 11  and R 12  are members independently selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroaryl, or R 10  and R 11  are optionally joined together to form a ring system having from 5 to 7 members;  
 R 13  is a leaving group;  
 with an organometallic species, thereby forming a compound according to Formula XVI:  
                     
 wherein,  
 R 14  is a member selected from the group consisting of substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl, in the presence of a catalyst effective at catalyzing coupling between a benzylic carbon atom of a compound according to Formula XV and an organometallic species.  
 
     
     
         69 . The method according to  claim 68 , wherein said organometallic species is of formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 L is an organometallic ligand;  
 M is a metal;  
 p is a member selected from the group consisting of the integers from 1 to 5, wherein each of said p organometallic ligands is independently selected;  
 n is a member selected from the group consisting of the integers from 0 to 13.  
 
     
     
         70 . The method according to  claim 69 , wherein each of R 10  and R 11  are methoxy.  
     
     
         71 . The method according to  claim 69 , wherein n is a member selected from the integers from 3 to 9.  
     
     
         72 . The method according to  claim 69 , wherein R 14  is a halogen.  
     
     
         73 . The method according to  claim 70 , wherein R 14  is chloro.  
     
     
         74 . A compound of formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1 , R 2  and R 3  are independently selected C 1 -C 6  alkyl groups;  
 R 4 is substituted or unsubstituted alkyl; and  
 R 5  is a member selected from branched, unsaturated alkyl and —CH 2 Y, in which Y is OR 6 , SR 6 , NR 6 R 7 , or a leaving group;  
 R 6  and R 7  are members independently selected from H and branched, unsaturated alkyl.  
 
     
     
         75 . The compound according to  claim 74 , wherein Y is halogen.  
     
     
         76 . The compound according to  claim 74 , wherein each of R 1 , R 2  and R 3  is methyl.  
     
     
         77 . The compound according to  claim 74 , wherein at least one of R 5 , R 6  and R 7  has the formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 n is a member selected from the integers from 0 to 13.  
 
     
     
         78 . The compound according to  claim 77  wherein n is a member selected from the integers from 3 to 9.  
     
     
         79 . A compound of formula:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1 , R 2  and R 3  are independently selected C 1 -C 6  alkyl groups;  
 R 4  is a protecting group which, together with the phenol oxygen to which it is attached is a member selected from ester, carbonate and phosphinate; and R 5  is —C(O)H.  
 
     
     
         80 . The compound according to  claim 79 , wherein each of R 1 , R 2  and R 3  is methyl.  
     
     
         81 . A compound having a structure of formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1 , R 2  and R 3  are independently selected C 1 -C 6  alkyl groups;  
 X +  is a cation; and  
 n is an integer from 0 to 13.