Method for preparing an R- or S-form of α-substituted heterocyclic carboxylic acid and a counter enantiomeric form of α-substituted heterocyclic carboxylic acid ester thereto using enzyme

A method for preparing an R- or S-form α-substituted heterocyclic carboxylic acid and a counter enantiomeric form of α-substituted heterocyclic carboxylic acid ester thereto, comprising the steps of:

• reacting a racemic α-substituted heterocyclic carboxylic acid with alcohol to give a racemic α-substituted heterocyclic carboxylic acid ester having the following chemical formula 1:
• wherein,
• R1 is selected from the group consisting of substituted or unsubstituted alkyl or alkenyl containing 1 to 6 carbon atoms, benzyl, cycloalkyl containing 3 to 6 carbon atoms, substituted or unsubstituted arylalkyl, and substituted or unsubstituted heteroarylalkyl, X represents O, S or NH, and n is an integer of 1 to 3;
• optically resolving the racemate of the formula 1 in an aqueous solution by use of an enzyme with enantioselectivity to hydrolyze either R-form or S-form of the racemate, thereby producing an R-form or S-form of α-substituted heterocyclic carboxylic acid and a counter enantiomeric form of α-substituted heterocyclic carboxylic acid ester thereto, said enzyme existing as a powder or an aqueous solution;
• extracting the unhydrolyzed α-substituted heterocyclic carboxylic acid ester of the racemate with an organic solvent, followed by recovering the α-substituted heterocyclic carboxylic acid ester from the organic phase and the α-substituted heterocyclic carboxylic acid from the aqueous phase, respectively;
• and
• subjecting the recovered α-substituted heterocyclic carboxylic acid ester in an organic solvent to hydrogenation under a constant hydrogen partial pressure at a constant temperature in the presence of a palladium catalyst on carbon (Pd/C), followed by recovering the resulting α-substituted heterocyclic carboxylic acid.