Enzymatic conversion of epoxides

Abstract

The invention relates to a process for converting an epoxide to an alcohol. The process according to the invention is enzymatically catalyzed and highly enantioselective and regiospecific.

1 . A process for enzymatically converting an, optionally substituted, epoxide of the formula  
       
         
           
           
               
               
           
         
       
       wherein R 1  is hydrogen or an, optionally substituted, aromatic or aliphatic group, to a mixture of an optically enriched epoxide of the formula (1) and an optically enriched alcohol of the formula  
       
         
           
           
               
               
           
         
       
       wherein R 2  is chosen from the group of I, Cl, Br, CN, N 3 , NO 2 , NO 3 , SCN, OCN, OR′, NHR′, SR′, SnR′, SeR′, PR′ and CO 2 R′, wherein R′ is chosen from hydrogen, amino groups, hydroxyl groups, alkyl groups, aryl groups, aralkyl, alkenyl and cycloalkyl groups, which process comprises reacting the epoxide with an anionic nucleophile (R 2     −   ) in the presence of a halohydrin dehalogenase.  
     
     
         2 . A process according to  claim 1 , wherein the optically enriched alcohol is recovered.  
     
     
         3 . A process according to  claim 1 , wherein the optically enriched epoxide is recovered.  
     
     
         4 . A process according to any of the preceding claims, wherein the halohydrin dehalogenase is a polypeptide having the amino acid sequence of SEQ ID NO2, or a homologue or functional derivative thereof.  
     
     
         5 . A process according to  claim 4 , wherein the homologue has an amino acid sequence which is for at least 90% homologues to the amino acid sequence of SEQ ID NO 2.  
     
     
         6 . A process according to  claim 4  or  5 , wherein the halohydrin dehalogenase is derived from  Agrobacterium radiobacter  (CBS 750.97), Arthrobacter sp. strain AD2 or Mycobacteriun sp. strain GP1.  
     
     
         7 . A process according to any of the preceding claims, wherein the epoxide is converted from a mixture comprising both enantiomers of said epoxide.  
     
     
         8 . A process according to  claim 7 , wherein the mixture is a racemic mixture.  
     
     
         9 . A process according to any of the preceding claims, wherein R 1  is chosen from the group of optionally substituted alkyl, aryl, aralkyl, alkenyl, cycloalkyl, and alkoxy groups.  
     
     
         10 . A process according to  claim 9 , wherein R 1  comprises from 1 to 20 carbon atoms.  
     
     
         11 . A process according to  claim 9  or  10  wherein R 1  optionally comprises a substituent chosen from the group of amino groups, halogens, hydroxyl groups, cyano groups, azide groups, nitro groups, haloalkyl groups, acyl groups, alkoxy groups, phenoxy groups and carboxyl groups.  
     
     
         12 . A process according to any of the preceding claims, wherein the epoxide has the formula  
       
         
           
           
               
               
           
         
       
       wherein R 4  is chosen from Cl, Br and I.  
     
     
         13 . A process according  claim 12 , wherein the epoxide is epichlorohydrin, epiiodohydrin, or epibromohydrin.  
     
     
         14 . A process according to  claim 12  or  13 , wherein the alcohol is obtained in a yield higher than 50%.  
     
     
         15 . A process according to any of the claims  1 - 11 , wherein R 1  is an, optionally substituted, aromatic group.  
     
     
         16 . A process according to  claim 15 , wherein the epoxide has the formula:  
       
         
           
           
               
               
           
         
       
       wherein R 3  is an ortho-, meta-, or para-substituent chosen from the group of —NO 2 , —NH 2 , —CH 3 , —OCH 3 , —OCH 2 CH 3 , —OH, —F, —Cl, —Br, —I, —COOH and —CN.  
     
     
         17 . A process according to  claim 15  or  16 , wherein the anionic nucleophile is N 3     −   , NO 2     −   , or CN—.  
     
     
         18 . A process according to any of the preceding claims, wherein the epoxide is reacted in the form of a solid, suspension, solution or dispersion.  
     
     
         19 . A process according to  claim 18 , wherein the epoxide is present in an aqueous medium in an amount of from 0.01 to 20 wt. %, based on the combined weights of the aqueous medium and the epoxide.  
     
     
         20 . A process according to any of the preceding claims, wherein the temperature is between 0 and 60° C.  
     
     
         21 . A process according to any of the preceding claims, wherein the pH is between 3 and 12.