Enantioselective formal synthesis of pregabalin with bifunctional acid/base organocatalysts

Download

index.pdf

Date

2013

Author

Kapucu, Merve

Metadata

Show full item record

Item Usage Stats

252
views

83
downloads

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.

Subject Keywords

Pregabalin., Catalysis., Asymmetric synthesis., Enantioselective catalysis.

URI

http://etd.lib.metu.edu.tr/upload/12616702/index.pdf
https://hdl.handle.net/11511/23215

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

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...
Design, synthesis, molecular docking studies and biological evaluation of thiazole carboxamide derivatives as COX inhibitors Hawash, Mohammed; Jaradat, Nidal; Abualhasan, Murad; ŞÜKÜROĞLU, MURAT KADİR; Qaoud, Mohammed T.; Kahraman, Deniz Cansen; Daraghmeh, Heba; Maslamani, Leen; Sawafta, Mais; Ratrout, Ala; Issa, Linda (2023-12-01) Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the most commonly used class of medications worldwide for the last three decades. Objectives: This study aimed to design and synthesize a novel series of methoxyphenyl thiazole carboxamide derivatives and evaluate their cyclooxygenase (COX) suppressant and cytotoxic properties. Methods: The synthesized compounds were characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and were evaluated for their selectivity towards COX-1 and CO...
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...

Citation Formats

M. Kapucu, “Enantioselective formal synthesis of pregabalin with bifunctional acid/base organocatalysts,” M.S. - Master of Science, Middle East Technical University, 2013.