Research Article
Rasemik Propranololün Biyokatalitik Derasemizasyonuna Ses Ötesi Dalga ve Tepkime Parametrelerinin Etkisi
Abstract
Farmasötik açıdan önem taşıyan, özellikle kardiyovasküler hastalıkların tedavisinde yaygın olarak kullanılan β-blokerlar kiral maddelerdir. β-blokerların enantiyomerleri çoğunlukla farklı farmakokinetik ve farmakodinamik özelliklere sahiptir. Bu nedenle β-bloker enantiyomerlerinin ayrı ayrı kullanılması önem kazanmıştır. Bu çalışmada; yaygın olarak kullanılan β-blokerlardan biri olan propranololün enantiyomerik saflıkta üretimi amaçlanmaktadır. Bu amaç doğrultusunda, Rhizopus oryzae CBS 111718 mikroorganizması kullanılarak biyokatalitik derasemizasyon ile enantiyomerik saflıkta propranolol üretimi incelenmiştir. R. oryzae mikroorganizması ile farklı tepkime parametrelerinin (hücre parçalama yöntemi, substrat derişimi, tepkime ortamının pH’ı, süre gibi) tepkimeye etkisi incelenerek en uygun çalışma koşullarının belirlenmesi hedeflenmiştir. Tüm bu denemeler sonucunda en yüksek enantiyomerik aşırılık (% ee) ve dönüşüm (% C) değerleri; pH 7 olan tampon ortamında, 3 mM substrat derişiminde, 10 dakika ses ötesi dalga (SÖD) uygulandığı koşulda, 6 gün sonunda % ee=28,4; % C=60,2 olarak bulunmuştur.
References
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- Kamal A., Khanna G.B.R., Krishnaji T., Tekumalla V., Ramu R., New chemoenzymatic pathway for β-adrenergic blocking agents, Tetrahedron: Asymmetry, 16, 1485-1494, 2005.
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- Li B., Nie Y., Mu X.Q., Xu Y., De novo construction of multi-enzyme system for one-potderacemization of (R,S)-1-phenyl-1,2-ethanediol by stereoinversionof (S)-enantiomer to the corresponding counterpart, J. Mol. Catal. B: Enzym., 129, 21-28, 2016.
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- Li Y.L., Xu J.H., Xu Y., Deracemization of aryl secondary alcohols via enantioselective oxidation and stereoselective reduction with tandem whole-cell biocatalysts, J. Mol. Catal. B: Enzym., 64, 48-52, 2010.
- Kazıcı H.Ç., Mehmetoğlu Ü., Use of the plant as biocatalysts for producing enantiomerically pure seconder alcohol, Journal of the Faculty of Engineering and Architecture of Gazi University, 30, (1), 49-56, 2015.
- Solano D.S., Hoyos P., Hernaiz M.J., Alcantara A.R., Sanchez-Montero J.M., Industrial biotransformations in the synthesis of building blocks leading to enantiopure drugs, Bioresour. Technol., 115, 196-207, 2012.
Year 2018,
Volume: 33 Issue: 2, 575 - 584, 06.04.2018
Abstract
References
- Agustian J., Kamaruddin A.H., Bhatia S., Single enantiomeric β-blockers-The existing Technologies, Process Biochem., 45, 1587-1604, 2010.
- Lund I.T., Bockmann P.L., Jacobsen E.E., Highly enantioselective CALB-catalyzed kinetic resolution of building blocks for β-blocker atenolol, Tetrahedron, 72, 7288-7292, 2016.
- Mehvar R., Brocks D.R., Stereospecific Pharmacokinetics and Pharmacodynamics: Cardiovascular Drugs (Chapter 7), Chirality in drug design and development, Editors; Reddy I.K. and Mehvar R., Marcel Dekker, New York, 281-350, 2004.
- Zelaszczyk D., Kononowicz K.K., Biocatalytic approaches to optically active β-blockers, Curr. Med. Chem., 14, 53-65, 2007.
- Kennedy H.L., Current utilization trends for β-blockers in cardiovascular disease, The American Journal of Medicine, 110 (5A), 2S-6S, 2001.
- Agrawal Y.K., Patel R.N., Chiral chromatographic seperation of β-blockers, Journal of Chromatograhy B, 820, 23-31, 2005.
- Kamal A., Khanna G.B.R., Krishnaji T., Tekumalla V., Ramu R., New chemoenzymatic pathway for β-adrenergic blocking agents, Tetrahedron: Asymmetry, 16, 1485-1494, 2005.
- Santoro M.I.R.M., Cho H.S., Kedor-Hackmann E.R.M., Enantiometric separation and quantitative determination pf propranolol in tablets bu chiral high-performance liquid chromatography, Drug Dev. Ind. Pharm., 27 (7), 693-697, 2001.
- Kamal A., Sandbhor M., Shaik A.A., Chemoenzymatic synthesis of (S) and (R)-propranolol and sotalol employing one-pot lipase resolution protocol, Bioorganig & Medicinal Chemistry Letters, 14, 4581-4583, 2004.
- Escorcia A.M., Molina D., Daza M.C., Doerr M., Acetylation of (R,S)-propranolol catalyzed by Candida antarctica lipaseB: An experimental and computational study, J. Mol. Catal. B: Enzym., 98, 21-29, 2013.
- Stoschitzky K., Lindner W., Zernig G., Racemic beta-blockers- fixed combinations of different drugs, Journal of Clinical and Basic Cardiology, 1 (1), 15-19, 1998.
- Kong X.D., Yu H.L., Yang S., Zhou J., Zeng B.B., Xu J.H., Chemoenzymatic synthesis of (R)- and (S)-propranolol using anengineered epoxide hydrolase with a high turnover number, J. Mol. Catal. B: Enzym., 122, 275-281, 2015.
- Li B., Nie Y., Mu X.Q., Xu Y., De novo construction of multi-enzyme system for one-potderacemization of (R,S)-1-phenyl-1,2-ethanediol by stereoinversionof (S)-enantiomer to the corresponding counterpart, J. Mol. Catal. B: Enzym., 129, 21-28, 2016.
- Damle S.V., Patil P.N., Salunkhe M.M., Biotransformations with Rhizopus arrhizus and Geotrichum candidum for the preparation of (S)-Atenolol and (S)-Propranolol, Bioorganic&Medicinal Chemistry, 8, 2067-2070, 2000.
- Li Y.L., Xu J.H., Xu Y., Deracemization of aryl secondary alcohols via enantioselective oxidation and stereoselective reduction with tandem whole-cell biocatalysts, J. Mol. Catal. B: Enzym., 64, 48-52, 2010.
- Kazıcı H.Ç., Mehmetoğlu Ü., Use of the plant as biocatalysts for producing enantiomerically pure seconder alcohol, Journal of the Faculty of Engineering and Architecture of Gazi University, 30, (1), 49-56, 2015.
- Solano D.S., Hoyos P., Hernaiz M.J., Alcantara A.R., Sanchez-Montero J.M., Industrial biotransformations in the synthesis of building blocks leading to enantiopure drugs, Bioresour. Technol., 115, 196-207, 2012.
There are 17 citations in total.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Engineering |
| Journal Section | Makaleler |
| Authors | |
| Publication Date | April 6, 2018 |
| Submission Date | November 20, 2016 |
| Acceptance Date | August 10, 17 |
| Published in Issue | Year 2018 Volume: 33 Issue: 2 |