Chemo-enzymatic approach to the synthesis of the antithrombotic clopidogrel

Abstract

The ( S)-2-chlorophenylglycine moiety is well recognized in the structure of ( S)-clopidogrel, a known antithrombotic drug. We prepared an enantiomerically pure chiral building block via an enzyme-catalyzed resolution of ( RS)- N-Boc-2-chlorophenylglycine methylester. The best results were obtained by means of an immobilized subtilisin, the cross-linked enzyme aggregate (Alcalase-CLEA®). The high enantiomeric excess of the synthon obtained remained the same over the course of clopidogrel synthesis; the simplicity of the process makes this pathway suitable for large-scale preparation.