Development of the commercial process for Zoloft®/sertraline
- 18 March 2005
- Vol. 17 (S1) , S120-S126
- https://doi.org/10.1002/chir.20113
Abstract
Sertraline represented Pfizer's first product with stereocenters not derived from natural sources, as was the case with azithromycin and β-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. Chirality 17:S120–S126, 2005.Keywords
This publication has 13 references indexed in Scilit:
- Asymmetric Catalysis in the Pharmaceutical IndustryAngewandte Chemie International Edition in English, 2004
- Review of sertraline and its clinical applications in psychiatric disordersExpert Opinion on Pharmacotherapy, 2001
- A combined synthetic and ab initio study of chiral oxazaborolidines structure and enantioselectivity relationshipsJournal of the American Chemical Society, 1994
- A practical enantioselective synthesis of .alpha.,.alpha.-diaryl-2-pyrrolidinemethanol. Preparation and chemistry of the corresponding oxazaborolidinesThe Journal of Organic Chemistry, 1991
- Friedel-Crafts synthesis of 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone, a key intermediate in the preparation of the antidepressant sertralineThe Journal of Organic Chemistry, 1990
- Highly enantioselective borane reduction of ketones catalyzed by chiral oxazaborolidines. Mechanism and synthetic implicationsJournal of the American Chemical Society, 1987
- Nontricyclic antidepressant agents derived from cis- and trans-1-amino-4-aryltetralinsJournal of Medicinal Chemistry, 1984
- Asymmetric reduction of aromatic ketones with the reagent prepared from (S)-(–)-2-amino-3-methyl-1,1-diphenylbutan-1-ol and boraneJournal of the Chemical Society, Chemical Communications, 1983
- Pyridazine Derivatives. I. Some Amebacidal 3-PyridazonesJournal of the American Chemical Society, 1953
- Amine Bisulfites. II. Their Use as Resolving Agents for Aldehydes and KetonesJournal of the American Chemical Society, 1949