Studies on the chemoenzymatic synthesis of 3-phenyl-GABA and 4-phenyl-pyrrolid-2-one: the influence of donor of the alkoxy group on enantioselective esterification

A new chemoenzymatic method for the synthesis of enantiomerically pure 3-phenyl-γ-aminobutyric acid 1 and 4-phenyl-pyrrolid-2-one 9 based on the enzymatic kinetic resolution of 3-phenyl-4-pentenoic acid 2 is described herein. Enzymatic resolution of the racemic substrate provided products with good enantioselectivity upon esterification. In these reactions, a new class of alkoxy group donor—orthoesters, acetals and ketals were used. The best results of the enzymatic kinetic resolution were obtained for triethyl orthoacetate in toluene solvent.

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Ethyl 3-phenyl-4-pentenoateC13H16OChiralcel OD-H; hexan/i-propanol; 9/1; 1 mL/min; 232 nm; tR(S) = 9.77 min; tR(R) = 11.03 min[α]D = −5.5 (c 0.5, CHCl3)Source of chirality: enzymatic esterificationAbsolute configuration: (S)

(S)-3-Phenyl-4-aminobutyric acid hydrochlorideC10H14NO2[α]D = −0.7 (c 1.0, H2O)Source of chirality: enzymatic esterificationAbsolute configuration: (S)

(S)-(+)-4-Phenyl-2-pyrollidoneC10H11NO[α]D = +7.0 (c 0.5, EtOH)Source of chirality: enzymatic esterificationAbsolute configuration: (S)