Enantioselective formal synthesis of pregabalin with bifunctional acid/base organocatalysts


Thesis Type: Postgraduate

Institution Of The Thesis: Middle East Technical University, Faculty of Arts and Sciences, Department of Chemistry, Turkey

Approval Date: 2013

Thesis Language: English

Student: Merve Kapucu

Supervisor: CİHANGİR TANYELİ

Abstract:

Pregabalin, which is marketed under the brand name of Lyrica by Pfizer, is an important chiral drug in the treatment of epilepsy and neuropathic pain. Since only S-Pregabalin is active for the treatment, asymmetric synthesis was accomplished in 6 steps and the chiral induction was done by transition metal catalysis in industrial production. In this thesis, we applied an alternative synthetic route taken place in 3 steps. The key step comprised the chiral induction done by organocatalysis and the formal asymmetric synthesis of Pregabalin has been performed by Michael type addition of diethyl malonate to (E)-4-Methyl-1-nitro-1-pentene in 81% ee. Parallel to this work, different Michael acceptors and donors were used to test our catalyts’ activities.