Method of producing fr901228

Abstract

Depsipeptides and congeners thereof are disclosed having structure (I), wherein m, n, p, q, X, R1, R2 and R3 are as defined herein. These compounds, including FR901228, have activity as, for example, immunosuppressants, as well as for the prevention or treatment of patients suffering or at risk of suffering from inflammatory, autoimmune or immune system-related diseases including graft-versus-host disease and enhancement of graft/tissue survival following transplant. Also provided are methods for inhibiting lymphocyte activation, proliferation, and/or suppression of IL-2 secretion.

1 . A method comprising:
 providing a type A crystalline form of compound FR901228:   
     
       
         
         
             
             
         
       
       formulating the type A crystalline form to produce a pharmaceutical composition. 
     
   
   
       2 . The method of  claim 1 , wherein the type A crystalline form is obtained from an ethanol/water mixture. 
   
   
       3 . A method comprising:
 providing a crystalline form of compound FR901228:   
     
       
         
         
             
             
         
       
       which crystalline form is characterized by a powder X-ray diffraction pattern substantially similar to  FIG. 3 , and 
       formulating the crystalline form to produce a pharmaceutical composition. 
     
   
   
       4 . The method of  claim 3 , wherein the crystalline form is characterized by having one or more peaks in its powder X-ray diffraction pattern selected from those at about 9.6, about 13.6, about 14.6, and about 17.4 degrees 2-theta. 
   
   
       5 . A method comprising:
 providing a crystalline form of compound FR901228:   
     
       
         
         
             
             
         
       
       which crystalline form is characterized by a powder X-ray diffraction pattern substantially similar to  FIG. 4 , and 
       formulating the crystalline form to produce a pharmaceutical composition. 
     
   
   
       6 . The method of  claim 1 , wherein the type A crystalline form is obtained from an acetone/water mixture. 
   
   
       7 . The method of  claim 1 , wherein the crystalline form is formulated as a pharmaceutical composition for treating cancer. 
   
   
       8 . The method of  claim 3 , wherein the crystalline form is formulated as a pharmaceutical composition for treating cancer. 
   
   
       9 . The method of  claim 5 , wherein the crystalline form is formulated as a pharmaceutical composition for treating cancer. 
   
   
       10 . A method comprising:
 subjecting a type A crystalline form of compound FR901228:   
     
       
         
         
             
             
         
       
       to one or more procedures selected from the group consisting of solvent extraction, concentration under reduced pressure, filtration, pH adjustment, adsorption treatment using an inorganic adsorbent, adsorption treatment using an adsorption resin, crystallization, or a combination thereof. 
     
   
   
       11 . A method comprising:
 subjecting a crystalline form of compound FR901228:   
     
       
         
         
             
             
         
       
       which crystalline form is characterized by a powder X-ray diffraction pattern substantially similar to  FIG. 3 , to one or more procedures selected from the group consisting of solvent extraction, concentration under reduced pressure, filtration, pH adjustment, adsorption treatment using an inorganic adsorbent, adsorption treatment using an adsorption resin, crystallization, or a combination thereof. 
     
   
   
       12 . A method comprising:
 subjecting a crystalline form of compound FR901228:   
     
       
         
         
             
             
         
       
     
     which crystalline form is characterized by a powder X-ray diffraction pattern substantially similar to  FIG. 4 , to one or more procedures selected from the group consisting of solvent extraction, concentration under reduced pressure, filtration, pH adjustment, adsorption treatment using an inorganic adsorbent, adsorption treatment using an adsorption resin, crystallization, or a combination thereof.