Chemo-enzymatic approach to the synthesis of the antithrombotic clopidogrel

A (S)-2-chlorophenylglycine moiety is well recognized in the structure of (S)-clopidogrel, a known antithrombotic drug. We prepared this chiral building block optically pure through an enzyme-catalyzed resolution of (R,S)-N-Boc-2-chlorophenylglycine methylester, the best results being obtained by means of an immobilized subtilisin, the cross-linked enzyme aggregate (Alcalase-CLEA®). The high value of enantiomeric excess of the obtained synthon kept unaltered in the course of clopidogrel synthesis and the process simplicity make this pathway suitable also for large scale preparations.