Methods for preparation and use of psorospermin analogs

Abstract

Psorospermin is a cytotoxic dihydrofuranoxanthone that has found to exhibit significant activity against various tumor cell lines. Unfortunately, psorospermin is no longer readily available from its natural plant source. The present invention is directed to a method for preparing psorospermin and psorospermin analogs. Methods are also disclosed for utilizing psorospermin analogs to inhibit cellular proliferation.

1 . A compound of formula:  
     
       
         
         
             
             
         
       
       wherein:  
       each of R 1 -R 4  and R 6  is independently H, OH, O-alkyl, halogen, or alkyl;  
       R 5  is H or alkyl; and  
       R 8  is H or alkyl.  
     
   
   
       2 . The compound of  claim 1 , wherein R 6  is H.  
   
   
       3 . The compound of  claim 1 , wherein R 2 -R 4  and R 6  are H.  
   
   
       4 . The compound of  claim 3 , wherein R 8  is methyl.  
   
   
       5 . The compound of  claim 1 , wherein the formula (3) has a configuration of:  
     
       
         
         
             
             
         
       
     
   
   
       6 . The compound of  claim 5 , wherein R 6  is H.  
   
   
       7 . The compound of  claim 5 , wherein R 2 -R 4  and R 6  are H.  
   
   
       8 . The compound of  claim 7 , wherein R 8  is methyl.  
   
   
       9 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier.  
   
   
       10 . A pharmaceutical composition comprising a compound of  claim 5  and a pharmaceutically acceptable carrier.  
   
   
       11 . A compound of the following formula:  
     
       
         
         
             
             
         
       
       wherein:  
       each of R 1 -R 4  and R 6  is independently H, OH, O-alkyl, halogen, or alkyl;  
       R 5  is H or alkyl;  
       R 7  is CH 2 ; and  
       R 8  is H or alkyl.  
     
   
   
       12 . The compound of  claim 11 , wherein R 6  is H.  
   
   
       13 . The compound of  claim 11 , wherein R 2 -R 4  and R 6  are H.  
   
   
       14 . The compound of  claim 13 , wherein R 8  is methyl.