Download PDF
Synfacts 2011(12): 1274-1274  
DOI: 10.1055/s-0031-1289313
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Crizotinib (PF-02341066)

Contributor(s): Philip Kocienski
P. D. de Koning et al.*
Pfizer Global Research and Development, Sandwich, UK; Pfizer Global Research and Development, Ann Arbor, San Diego and Groton, USA
Further Information

Publication History

Publication Date:
18 November 2011 (online)

    Permissions and Reprints

Significance

Crizotinib (PF-02341066) is a cMet/ALK inhibitor that is in phase III clinical trials for the treatment of cancer. A key step in the synthesis is the asymmetric reduction of acetophenone A to (S)-B using an engineered ketoreductase from Lactobacillus sp. The engineered ketoreductase has reversed enantioselectivity compared with the wild-type enzymes. The reversed enantioselectivity was achieved by mutating the tyrosine residue at position 190 to a proline.