Enantioselective formal synthesis of pregabalin with bifunctional acid/base organocatalysts

Download
2013
Kapucu, Merve
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.

Suggestions

Concentratıon Dependent Effects Of Celecoxibe On Model Membranes
Banerjee, Sreeparna(2009-12-31)
Celecoxib is a new generation non-steroidal anti- inflammatory drug that selectively inhibits cyclooxygenase-2 and has reduced side effects because of its selectivity. Celecoxib has also been shown to have anti-cancer activity in several cancer types but its action of mechanism is not well understood. Since biological membranes are extremely complex structures, studying the effects of drugs on simple model membranes would be a convenient way to investigate drug-membrane interactions. Fourier Transform Infra...
Squaramide catalyzed alpha-chiral amine synthesis
Karahan, SEDA; Tanyeli, Cihangir (2018-10-17)
Enantiomerically pure alpha-chiral amines, have been commonly utilized as resolving agents and chiral auxiliaries and are currently found in 40% of active pharmaceutical ingredients. Hence, development of highly stereoselective metal-free protocols regarding atom-economy and large-scale applications becomes a major issue. In this respect, chiral bifunctional H-bonding squaramides have been successfully applied for both amine synthesis and functionalization of amines in the last decade. This survey summarize...
Enantioselective Michael addition of malononitrile to chalcone with bifunctional squaramide organocatalysts
Sargın, Nurdan; Tanyeli, Cihangir; Department of Chemistry (2015)
4H-pyran derivatives show diverse biological activity such as antimicrobial, antibacterial, antiviral and antifungal. 4H-pyran derivatives can be synthesized easily from 2-(3-oxo-1,3-diphenylpropyl)malononitrile which is the Michael addition product of malononitrile to trans-chalcone. Synthesizing chiral biologically active compounds with metal free approach (organocatalysis) is a significant topic. In this thesis, chiral 2-(3-oxo-1,3-diphenylpropyl)malononitrile was synthesized with quinine or 2-aminoDMAP ...
Structural effects of simvastatin on liver rate tissue: Fourier transform infrared and Raman microspectroscopic studies
Garip, Sebnem; Bayari, Sevgi Haman; Severcan, Mete; Abbas, Sherif; Lednev, Igor K.; Severcan, Feride (2016-02-01)
Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simva...
Metformin – Cisplatin Combination Treatment Alters mRNA Expression of Hexokinase II Gene in LNCaP and PC3 Prostate Cancer Cell Lines
Durukan, Özlem; Evin, Emre; Arslan, Şevki; Adalı, Orhan (null; 2017-07-08)
Metformin is an antidiabetic drug with anticancer properties. Cisplatin is known as one of the most potent chemotherapeutics for treatment of various types of cancer. In order to overcome cisplatin resistance and toxicity, the drug can be combined with other chemotherapeutics that sensitize tumour cells to cisplatin. The ability of metformin to potentiate cisplatin-mediated killing of cancer cells in vitro, makes it a plausible candidate for combination with cisplatin-based therapy. The aim of this study is...
Citation Formats
M. Kapucu, “Enantioselective formal synthesis of pregabalin with bifunctional acid/base organocatalysts,” M.S. - Master of Science, Middle East Technical University, 2013.