Process for the enantioselective reduction of 8-chloro-6-oxo-octanoic acid alkyl esters

Abstract

The invention relates to a process for the production of (R)- or (S)-8-chloro-6-hydroxyoctanoic acid alkyl esters of the general formula (R)-II or (S)-II, in which R means C 1-4 alkyl, from 8-chloro-6-oxo-octanoic acid alkyl esters of the general formula I, in which R has the above meaning. The desired enantiomers are produced biocatalytically in an enantioselective reduction, wherein as desired the strains Mucor racemosus are used for (S)-II compounds and Geotrichum candidum for (R)-II compounds. The resultant esters may, in known manner, be converted stereospecifically into (R)-α-lipoic acid.

1 . (canceled)  
   
   
       2 . A process for the production of (S)-8-chloro acid alkyl esters of the formula (S)-II from 8-chloro-6-oxo-octanoic acid alkyl esters of the formula I,  
     
       
         
         
             
             
         
       
       in which R in each case means C 1-4  alkyl, wherein the reaction is performed by means of a biocatalyst.  
     
   
   
       3 . (canceled)  
   
   
       4 . The process according to  claim 2 , wherein a strain of the species  Geotrichum candidum  is used as the biocatalyst.  
   
   
       5 . (canceled)  
   
   
       6 . The process according to  claim 2 , wherein a strain of the species  Mucor racemosus  is used as the biocatalyst.  
   
   
       7 . A process according to  claim 2 , wherein  Mucor racemosus  of the specific strain (DSM 13775) is used.  
   
   
       8 . A process according to  claim 2 , wherein a medium is used for biotechnological production, which medium contains a carbon source, an inorganic nitrogen source together with further nutrient salts.  
   
   
       9 . A process for the production of (R)-8-chloro-6-hydroxyoctanoic acid alkyl esters or (S)-8-chloro-6-hydroxyoctanoic acid alkyl esters of the formula IIb from 8-chloro-6-oxo-octanoic acid of formula I,  
     
       
         
         
             
             
         
       
       wherein:  
       the 8-chloro-6-oxo-octanoic acid of formula I is converted to (R)-8-chloro-6-hydroxyoctanoic acid or (S)-8-chloro-6-hydroxyoctanoic acid of the formula IIa by means of a biocatalyst;  
       the (R)-8-chloro-6-hydroxyoctanoic acid or (S)-8-chloro-6-hydroxyoctanoic acid of the formula IIb is converted by esterification into the alkyl ester of the formula (R)-IIb or (S)-IIb, in which R in each case means C 1-4  alkyl; and  
       isolating and recovering the (R)-8-chloro-6-hydroxyoctanoic acid alkyl esters or (S)-8-chloro-6-hydroxyoctanoic acid alkyl esters of the formula IIb.