Microbiological process for enantioselective (S)-hydroxylation

Abstract

The invention relates to a microbiological process for preparing chiral arylalkanols by enantioselectively hydroxylating arylalkanes in the presence of a microorganism's host cells which are expressing the genes for oxygenases.

What is claimed is:  
     
         1 . A process for preparing (S)-1-homoarylalkan-1-ols or (S)-1-heteroarylalkan-1-ols by enantioselectively hydroxylating 1-homoarylalkanes or 1-heteroarylalkanes, which comprises carrying out the hydroxylation in the presence of a microorganism which contains nucleic acids which encode an oxygenase which catalyses the enantioselective (S)-hydroxylation.  
     
     
         2 . The process as claimed in  claim 1 , wherein the hydroxylation is carried out in the presence of a transformed microorganism which contains nucleic acids which encode an oxygenase.  
     
     
         3 . The process as claimed in  claim 1 , wherein the hydroxylation is carried out in the presence of bacteria, yeast or fungi which contain nucleic acids which encode an oxygenase.  
     
     
         4 . The process as claimed in  claim 1 , wherein the hydroxylation is carried out in the presence of Gram-negative bacteria.  
     
     
         5 . The process as claimed in  claim 1 , wherein the hydroxylation is carried out in the presence of Gram-negative bacteria of the genus Pseudomonas, Rhodopseudomonas, Burkholderia, Ralstonia, Comamonas, Acinetobacter, Rhizobium or  Escherichia coli.    
     
     
         6 . The process as claimed in  claim 1 , wherein the hydroxylation is carried out in the presence of an  Escherichia coli  K12 strain or of a  Pseudomonas putida  strain.  
     
     
         7 . The process as claimed in  claim 1 , wherein the microorganisms contain nucleic acids which encode a naphthalene dioxygenase.  
     
     
         8 . The process as claimed in  claim 1 , wherein the microorganisms contain nucleic acids which encode a naphthalene dioxygenase from  Pseudomonas putida  G7 (DSM 4476) or Pseudomonas sp. NCIB 9816 (DSM 8368) or similar enzymes possessing at least 70% identity over the total length of the amino acid sequence.  
     
     
         9 . The process as claimed in  claim 1 , wherein the starting compounds employed are (C 1 -C 6 )-alkyl-(C 5 -C 14 )-aromatics which are ring-substituted once or more than once, identically or differently, and in which from 0 to 3 carbon atoms are replaced, in the aromatic ring system, with heteroatoms from the group N, O and/or S.  
     
     
         10 . The process as claimed in  claim 1 , wherein the starting compounds employed are (C 1 -C 6 )-alkyl-(C 5 -C 6 )-aromatics which are ring-substituted once or more than once, identically or differently, and in which from 0 to 3 carbon atoms are replaced, in the aromatic ring system, with heteroatoms from the group N, O and/or S.  
     
     
         11 . The process as claimed in  claim 1 , wherein (S)-1-homoarylalkan-1-ols of the general formula (I)  
       
         
           
           
               
               
           
         
       
       where 
 R 1  is C 1 -C 3 -alkyl,  
 R 2 , R 3 , R 4 , R 5  and R 6  are, independently of each other, H, halogen, C 1 -C 4 -haloalkyl, C1-C 4 -alkyl, hydroxyl, C 1 -C 4 -alkoxy, thiol, C 1 -C 4 -thioalkoxy, amino or primary or secondary C 1 -C 4 -aminoalkyl, or at least one radical R 2  to R 6  is different from H  
 are prepared by enantioselectively hydroxylating compounds of the general formula I,  
                     
 where  
 R 1  has the meaning mentioned for formula I, and  
 R 2 , R 3 , R 4 , R 5  and R 6  have, independently of each other, the meaning mentioned for formula I.  
 
     
     
         12 . The process as claimed in  claim 11 , wherein R 1  is C 1 -C 3 -alkyl and R 2 , R R 4 , R 5 -and R are, independently of each other, H, halogen or C 1 -C 4 -haloalkyl, or at least one radical R 2  to R 6  is different from H.  
     
     
         13 . The process as claimed in  claim 11 , wherein R 1  is methyl.