Family of canadensol taxanes, the semi-synthetic preparation and therapeutic use thereof

Abstract

The present invention relates to a new taxane having the structure as in formula I and its analogs as depicted in Formula II and Formula III. The invention includes novel semisynthetic and isolation methods for the preparation of these novel taxanes. Specifically, the present invention relates to the new taxane Canadensol isolated from plants of the Taxus genus, in particular, Taxus canadensis . The present invention further relates to the use of these new taxanes as anticancer agents.

We claim:  
     
         1 . A compound of formula III:  
       
         
           
           
               
               
           
         
       
       wherein R 3  is selected from the group consisting of propyl, isopropyl and n-butyl.  
     
     
         2 . The compound as in  claim 1 , wherein R 3  is isopropyl.  
     
     
         3 . A compound of formula IV:  
       
         
           
           
               
               
           
         
       
       wherein R 3  is selected from the group consisting of propyl, isopropyl and n-butyl.  
     
     
         4 . The compound as in  claim 3 , wherein R 3  is isopropyl.  
     
     
         5 . A compound of formula V:  
       
         
           
           
               
               
           
         
       
       wherein R 4  is SiEt 3  or CO 2 CH 2 CCl 3 .  
     
     
         6 . A process for the preparation of a compund of formula V, which comprises the steps of: 
 (i) protecting a hydroxy group at the 7 position of baccatin III:                          to form a 7-OH-protected baccatin III;    and    (ii) reacting the 7-OH-protected baccatin III with a compound of formula VII.                          
     
     
         7 . The process of  claim 6 , wherein the hydroxy group at the 7 position is protected with SiEt 3  or CO 2 CH 2 CCl 3 .  
     
     
         8 . A method of inhibiting tumours in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound of formula III:  
       
         
           
           
               
               
           
         
       
       wherein R 3  is selected from the group consisting of propyl, isopropyl and n-butyl.  
     
     
         9 . The method of  claim 8 , wherein R 3  is isopropyl.  
     
     
         10 . A pharmaceutical formulation comprising one or more compounds of formula III:  
       
         
           
           
               
               
           
         
       
       and a pharmaceutically acceptable carrier; wherein R 3  is selected from the group consisting of propyl, isopropyl and n-butyl.  
     
     
         11 . The pharmaceutical formulation of  claim 10 , wherein R 3  is isopropyl.