Development of the commercial process for Zoloft/sertraline.

Sertraline represented Pfizer's first product with stereocenters not derived from natural sources, as was the case with azithromycin and beta-lactam products. Discovery chemists employed chromatography and classical resolution to secure the active agent's two stereocenters. Investigations to identify a commercial route comprised a number of synthetic approaches, including enantioselective ketone reduction, SN2 displacement of an activated alcohol to transfer chirality, and continuous chromatography. The challenges of adopting new technology in the pharmaceutical industry are discussed in the context of sertraline's development. The successful outcome employed continuous chromatography, and the potential for this technology to shift the development paradigm for any development candidate or commercial product is described. 2004 Wiley-Liss, Inc.