Process for preparing 3-heteroaryl-3-hydroxypropanoic acid derivatives

Abstract

The invention relates to a process for preparing enantiomer-enriched 3-heteroaryl-3-hydroxypropanoic acid derivatives and 3-heteroaryl-1-aminopropan-3-ols, and to their use.

1 . A method for preparing a 3-hydroxy-3-(2-thienyl)propionamide of the formula:  
       heteroaryl-CH(OH)—CH 2 —CO—NR 2 R 3    
     wherein 
 heteroaryl represents 2-thiophenyl, which is optionally monosubstituted or polysubstituted by fluorine, chlorine, bromine, nitro, hydroxyl, C 1-8 -alkyl, C 1-4 -fluoroalkyl and C 1-4 -alkoxy; and  
 R 2  and R 3  are each independently hydrogen, C 1-8 -alkyl, C 4-10 -aryl or C 5-11 -arylalkyl;  
 which comprises:  
 a) reducing the compound of the formula:  
   heteroaryl-CO—CH 2 —CO—OR 1    
 wherein  
 heteroaryl is as defined above; and  
 R 1  represents hydrogen, C 1-8 -alkyl, C 4-10 -aryl or C 5-11 -arylalkyl;  
 in the presence of a microorganism and/or cell preparation;  
 to form the resulting compound of the formula:  
   heteroaryl-CH(OH)—CH 2 —CO—OR 1    
 and then  
 b) reacting said resulting compound with an amine of the formula:  
   HNR 2 R 3    
 wherein  
 R 2  and R 3  have the meanings given above.  
 
   
   
       2 . The method according to  claim 1 , wherein the microorganism is one selected from the group consisting of microorganisms of the genera  Saccharomyces, Geotrichum, Candida, Pichia, Hansenula, Yarrowia, Phizopus, Mortierella, Mucor, Sporotrichum, Rhodotorula, Trichoderma, Aspergillus, Penicillium, Pullaria, Cunninghamella  and  Curvularia.    
   
   
       3 . The method according to  claim 2 , wherein the microorganism is  Saccharomyces cereviseae.    
   
   
       4 . The method according to  claim 2 , wherein the microorganism is  Geotrichum candidum.    
   
   
       5 . A method for preparing an optically active 3-hydroxy-3-(2-thienyl)propionic acid ester compound of the formula:  
       heteroaryl-CH(OH)—CH 2 —CO—OR 1    
     wherein 
 heteroaryl represents 2-thiophenyl, which is optionally monosubstituted or polysubstituted by fluorine, chlorine, bromine, nitro, hydroxyl, C 1-8 -alkyl, C 1-4 -fluoroalkyl and C 1-4 -alkoxy; and  
 R 1  represents hydrogen, C 1-8 -alkyl, C 4-10 -aryl or C 5-11 -arylalkyl;  
 which comprises reducing the compound of the formula:  
   heteroaryl-CO—CH 2 —CO—OR 1    
 wherein  
 heteroaryl and R 1  are as defined above;  
 in the presence of a microorganism and/or cell preparation.  
 
   
   
       6 . The method according to  claim 5 , wherein the microorganism is one selected from the group consisting of microorganisms of the genera  Saccharomyces, Geotrichum, Candida, Pichia, Hansenula, Yarrowia, Phizopus, Mortierella, Mucor, Sporotrichum, Rhodotorula, Trichoderma, Aspergillus, Penicillium, Pullaria, Cunninghamella  and  Curvularia.    
   
   
       7 . The method according to  claim 6 , wherein the microorganism is  Saccharomyces cereviseae.    
   
   
       8 . The method according to  claim 6 , wherein the microorganism is  Geotrichum candidum.