Method of purifying pravastatin

Abstract

The present invention provides pure pravastatin compositions and pure compactin compositions, and methods for the preparation thereof.

1 - 48 . (canceled) 
   
   
       49 . A method of synthesizing a pravastatin batch comprising:
 (a) determining the level of compactin C in at least one batch of compactin that contains compactin C;   (b) selecting a compactin batch that contains compactin C in an amount that is about 0.16% or less by weight of the batch; and   (c) hydroxylating the selected compactin batch to synthesize a pravastatin batch.   
   
   
       50 . The method of  claim 49 , wherein the selected compactin batch from step (b) contains compactin C in an amount of about 0.15% to about 0.16% by weight of the batch. 
   
   
       51 . The method of  claim 49 , wherein the pravastatin batch is synthesized by fermentation of the compactin batch. 
   
   
       52 . The method of  claim 49 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.1% or less by weight of the batch. 
   
   
       53 . The method of  claim 52 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.02% to about 0.1% by weight of the batch. 
   
   
       54 . The method of  claim 52 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.04% or less by weight of the batch. 
   
   
       55 . The method of  claim 54 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.02% to about 0.04% by weight of the batch. 
   
   
       56 . The method of  claim 54 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.03% or less by weight of the batch. 
   
   
       57 . The method of  claim 56 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.02% or less by weight of the batch. 
   
   
       58 . A method of synthesizing a pravastatin batch comprising:
 a) purifying a compactin batch containing compactin C to obtain a compactin batch containing compactin C in an amount that is about 0.16% or less by weight of the composition; and   b) hydroxylating the compactin batch resulting from step a) to synthesize a pravastatin batch.   
   
   
       59 . The method of  claim 58 , wherein the purification in step a) comprises:
 i) dissolving or suspending the starting compactin batch in at least one water miscible organic solvent;   ii) adding water to the solution or suspension formed in step i) to obtain a mixture, wherein the volume ratio between the water and the water miscible organic solvent is about 0.16:1 to about 0.4:1; and   iii) precipitating the compactin batch containing compactin C in an amount that is about 0.16% or less by weight of the batch.   
   
   
       60 . A method of synthesizing a pravastatin batch comprising:
 a) dissolving or suspending a compactin batch containing compactin C in at least one water miscible organic solvent;   b) adding water to the solution or suspension formed in a) to obtain a mixture, wherein the volume ratio between the water and the water miscible organic solvent is about 0.16:1 to about 0.4:1;   c) precipitating the compactin batch;   d) determining the quantity of compactin C in the precipitated compactin batch from step c); and
 if the quantity of compactin C determined in step d) is greater than 0.16% by weight of the batch, then: 
   e1) purifying, by crystallization, the precipitated compactin batch until the quantity of compactin C is 0.16% or less by weight of the batch; and   f) hydroxylating the purified compactin batch from step e1) to synthesize pravastatin batch; or,
 if the quantity of compactin C determined in step d) is 0.16% or less by weight of the batch, then: 
   e2) hydroxylating the precipitated compactin batch to synthesize a pravastatin batch.   
   
   
       61 . The method of  claim 60 , wherein in step e1) the compactin batch is purified until the quantity of compactin C is about 0.15% or less by weight of the batch. 
   
   
       62 . The method of  claim 60 , wherein the pravastatin batch is synthesized by fermentation of the compactin batch. 
   
   
       63 . The method of  claim 60 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.1% or less by weight of the batch. 
   
   
       64 . The method of  claim 63 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.02% to about 0.1% by weight of the batch. 
   
   
       65 . The method of  claim 63 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.04% or less by weight of the batch. 
   
   
       66 . The method of  claim 65 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.02% to about 0.04% by weight of the batch. 
   
   
       67 . The method of  claim 65 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.03% or less by weight of the batch. 
   
   
       68 . The method of  claim 57 , wherein the synthesized pravastatin batch contains pravastatin C in an amount that is about 0.02% or less by weight of the batch. 
   
   
       69 . A method comprising: providing a compactin batch containing compactin C in an amount that is about 0.16% or less by weight of the batch; and hydroxylating the compactin batch, thereby forming a pure pravastatin batch. 
   
   
       70 . A method comprising: hydroxylating a compactin batch containing compactin C in an amount that is about 0.16% or less by weight of the batch, thereby forming a pure pravastatin batch.