Novel chiral heptyne derivatives for the preparation of epothilones and processes for their preparation

Abstract

The invention relates to a new synthetic process for the production of key intermediates useful in the synthesis of epothilones or epothilone derivatives, to certain compounds used to produce these key intermediates and to a process to produce said compounds.

1 . A process for preparing an epothilone or an epothilone derivative comprising reacting a compound represented by formula IA,  
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of hydrogen, alkyl, and substituted alkyl; and X 1  is an oxygen protecting group;  
         comprising reacting a compound of formula IV,  
         
           
             
             
                 
                 
             
           
         
         wherein X 1  is as defined above, with an aldehyde of formula V,  
           RCHO  V  
         wherein R is as defined above, in the presence of a suitable base to form a compound of formula III,  
         
           
             
             
                 
                 
             
           
         
         wherein R and X 1  are as defined above, reacting compound of formula III with a suitable oxidizing agent to form a compound of formula II,  
         
           
             
             
                 
                 
             
           
         
         wherein R and X 1  are as defined above, and subsequently reacting compound II with a suitable reducing agent to form said compound of formula IA.  
       
     
     
         2 . A process for preparing a compound represented by formula IA,  
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of hydrogen, alkyl, and substituted alkyl; and X 1  is an oxygen protecting group;  
         comprising reacting a compound of formula IV,  
         
           
             
             
                 
                 
             
           
         
         wherein X 1  is as defined above, with an activated acid derivative of formula VI,  
         
           
             
             
                 
                 
             
           
         
         wherein R is as described above; and X is a Weinreb residue, in the presence of a suitable base to form a compound of formula II,  
         
           
             
             
                 
                 
             
           
         
         wherein R and X 1  are as defined above, and subsequently reacting the compound of formula II with a suitable reducing agent to form said compound of formula IA.  
       
     
     
         3 - 13 . (canceled)  
     
     
         14 . A method of preparing an epothilone or an epothilone derivative comprising reacting a compound of formula II,  
       
         
           
           
               
               
           
         
         wherein:  
         R is selected from the group consisting of hydrogen, alkyl, and substituted alkyl; and, X 1  is an oxygen protecting group.  
       
     
     
         15 - 26 . (canceled)