Yeşil Çözücü Ortamında Enzimatik Kinetik Rezolüsyon Yöntemi ile Enantiyomerik Saflıkta 1-Feniletanol Üretimi

Yıl 2024, Cilt: 27 Sayı: 4, 1213 - 1222, 25.09.2024

Ayşe Bozan , Rahime Songür , Ülkü Mehmetoğlu

https://doi.org/10.2339/politeknik.740893

Öz

Çözücüler kimyasal proseslerdeki en kritik bileşenlerdendir. Bu yüzden çözücünün yapısı, maliyeti ve ulaşılabilir olması gibi önemli özelliklerinin yanı sıra güvenilir ve çevre dostu olması da gerekmektedir. Bu nedenle, son zamanlarda geleneksel çözücülerin yerini alabilecek yeşil çözücü arayışları hız kazanmıştır. Bu çalışmada değerli kimyasalların üretiminde önemli kiral yapı bloklarından olan 1-feniletanolün "yeşil çözücü ortamında" enantiyomerik saflıkta elde edilmesi amaçlanmış ve bu doğrultuda propilen karbonat (PK), dimetil karbonat (DMK) ve 2-metiltetrahidrofuran (MeTHF) kullanılmıştır. En iyi sonuçlar DMK kullanıldığında sağlanmış olup 240 mM substrat ve 20 mg/mL lipaz derişimlerinde, 40℃ ve 250 rpm’de gerçekleştirilen 3 saat reaksiyon sonunda substrat için %100 enantiyomerik aşırılık (ees) ile %50 dönüşüme ulaşılmıştır. Bu çalışma ile “en yeşil çözücülerden biri” olarak nitelendirilen DMK ilk kez rasemik 1-feniletanolün enzimatik kinetik rezolüsyonunda çözücü ortamı olarak kullanılmıştır. Sonuçlar, literatürde hem geleneksel hem de diğer yeşil çözücülerle gerçekleştirilen çalışmalarla karşılaştırıldığında DMK’nın düşük eko-toksikliği, biyo-bozunurluğu, düşük maliyetli olması gibi avantajlı özelliklerinin yanı sıra yüksek ees ve dönüşüm de sağlaması neticesinde bu çözücülerin yerine geçebileceğini göstermiştir.

Anahtar Kelimeler

Yeşil çözücü, dimetil karbonat, 1-feniletanol, kinetik rezolüsyon, Novozyme 435

Destekleyen Kurum

Ankara Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü

Proje Numarası

18H0443002

Teşekkür

Bu çalışma Ankara Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü tarafından 18H0443002 nolu proje ile desteklenmiştir.

The Production of Enantiomerically Pure 1-Phenylethanol in Green Solvent Media via Enzymatic Kinetic Resolution Method

Öz

Solvents are among the most critical components in chemical processes. For this reason, in addition to its important properties such as structure, cost and availability, a solvent must be also safe and environmentally friendly. Therefore, the research on the use of green solvents to replace the traditional ones have gained wide interest.1-phenylethanol is one of the important chiral building blocks which are used for producing fine chemicals in several industries. In this work, it was aimed to produce enantiomerically pure 1-phenylethanol in the green solvent media. Accordingly, propylene carbonate (PC), dimethyl carbonate (DMC) and 2-methyltetrahydrofuran (MeTHF) were used. Best results were obtained by using DMC. 100% enantiomeric excess for the substrate (ees) and 50% conversion were reached with 240 mM substrate concentration, 20 mg/mL lipase concentration and 3 hours reaction time at 40℃ and 250 rpm. In this work; DMC, which is characterized as “one of the greenest solvents”, was used as the reaction solvent for the first time in the enzymatic kinetic resolution of racemic 1-phenylethanol. When compared with the literature, in which both traditional and other green solvents were used, it was observed that DMC can replace these solvents, considering its advantageous properties such as low eco-toxicity, high biodegrability and low cost, together with its high ees and conversion values.

Anahtar Kelimeler

Green solvent, dimethyl carbonate, 1-phenylethanol, kinetic resolution, Novozyme 435

Proje Numarası

18H0443002

Kaynakça

• [1] Seddigi Z.S., Malik M.S., Ahmed S.A., Babalghith A.O. and Kamal A., “Lipases in asymmetric transformations: Recent advances in classical kinetic resolution and lipase-metal combinations for dynamic processes”, Coordination Chemistry Reviews, 348: 54-70, (2017).
• [2] Srinivas N.R., Barbhaiya R.H. and Midha K.K., “Enantiomeric Drug Development: Issues, Considerations and Regulatory Requirements”, Journal of Pharmaceutical Sciences, 90(9): 1205-1215, (2001).
• [3] Ahmed M., Kelly T. and Ghanem A., “Applications of enzymatic and non-enzymatic methods to access enantiomercally pure compounds using kinetic resolution and racemisation”, Tetrahedron, 68: 6781-6802, (2012). doi:10.1016/j.tet.2012.05.049.
• [4] Graber M., Rouillard H., Delatouche R., Fniter N., Belkhiria B., Bonnet A., Domon L. and Thiéry V., “Improved racemate resolution of pentan-2-ol and trans-(Z)-cyclooct-5-ene-1,2-diol by lipase catalysis”, Journal of Biotechnology, 238: 60-68, (2016).
• [5] Lang J.C. and Armstrong D.W., “Chiral surfaces : The many faces of chiral recognition”, Current Opinion in Colloid & Interface Science,32: 94-107, (2017).
• [6] Habulin M. and Knez Z., “Optimization of (R,S)-1-phenylethanol kinetic resolution over Candida antarctica lipase B in ionic liquids”, Journal of Molecular Catalysis B: Enzymatic, 58: 24-28, (2009). doi:10.1016/j.molcatb.2008.10.007.
• [7] Singh M., Singh R.S. and Banerjee U.C., “Enantioselective transesterification of racemic phenyl ethanol and its derivatives in organic solvent and ionic liquid using Pseudomonas aeruginosa lipase”, Process Biochemistry, 45: 25-29, (2010). doi:10.1016/j.procbio.2009.07.020.
• [8] Ghanem A. and Aboul-Enein H.Y., “Lipase-mediated chiral resolution of racemates in organic solvents”, Tetrahedron: Asymmetry, 78(15): 3331-3351, (2004).
• [9] Li X., Xu L., Wang G., Zhang H. and Yan Y., “Conformation studies on Burkholderia cenocepacia lipase via resolution of racemic 1-phenylethanol in non-aqueous medium and its process optimization”, Process Biochemistry, 48: 1905-1913, (2013).
• [10] Kamble M.P., Chaudhari S.A., Singhal R.S. and Yadav G.D., “Synergism of microwave irradiation and enzyme catalysis in kinetic resolution of (R,S)-1-phenylethanol by cutinase from novel isolate Fusarium ICT SAC1”, Biochemical Engineering Journal, 117: 121-128, (2017).
• [11] Suan C.L. and Sarmidi M.R., “Immobilised lipase-catalysed resolution of (R,S)-1-phenylethanol in recirculated packed bed reactor”, Journal of Molecular Catalysis B: Enzymatic, 28: 111-119, (2004). doi:10.1016/j.molcatb.2004.02.004.
• [12] Cazetta T, Moran P.J.S. and Rodrigues A.R., “Highly enantioselective deracemization of 1-phenyl-1,2-ethanediol and its derivatives by stereoinversion using Candida albicans in a one-pot process”, Journal of Molecular Catalysis B: Enzymatic, 109: 178-183, (2014).
• [13] Melais N, Zouioueche L.A. and Riant O., “The effect of the migrating group structure on enantioselectivity in lipase-catalyzed kinetic resolution of 1-phenylethanol”, C. R. Chimie, 19: 971-977, (2016).
• [14] Jurček O., Wimmerová M. and Wimmer Z., “Selected chiral alcohols: Enzymic resolution and reduction of convenient substrates”, Coordination Chemistry Reviews, 252: 767-781, (2008). doi:10.1016/j.ccr.2007.09.026.
• [15] Gupta S.M., Kamble M.P. and Yadav G.D., “Insight into microwave assisted enzyme catalysis in process intensification of reaction and selectivity: Kinetic resolution of (R, S)-flurbiprofen with alcohols”, Molecular Catalysis, 440: 50-56, (2017).
• [16] Basso A. and Serban S., “Industrial applications of immobilized enzymes – A review”, Molecular Catalysis, 479: 1-20, (2019).
• [17] Villalba M., Verdasco-Martín C.M., Santos J.C.S., Fernandez-Lafuente R. and Otero C., “Operational stabilities of different chemical derivatives of Novozym 435 in an alcoholysis reaction”, Enzyme and Microbial Technology, 90: 35-44, (2016).
• [18] Almeida J.M., Alnoch R.C., Souza E.M., Mitchell D.A. and Krieger N., “Metagenomics : Is it a powerful tool to obtain lipases for application in biocatalysis?”, BBA – Proteins and Proteomics, 1868: 1-13, (2020).
• [19] Gu Y. and Jérôme F., “Bio-based solvents: an emerging generation of fluids for the design of eco-efficient processes in catalysis and organic chemistry”, Chemical Society Reviews, 42: 9550-9570, (2013).
• [20] Schäffner B., Schäffner F., Verevkin S.P. and Börner A., “Organic Carbonates as Solvents in Synthesis and Catalysis”, Chemical Reviews, 110: 4554-4581, (2010).
• [21] Lozano P., Bernal J.M., Gómez C., Garcia Verdugo E., Burguete M.I., Sánchez G., Vaultier M. and Luis S.V., “Green bioprocesses in sponge-like ionic liquids”, Catalysis Today, 255: 54-59, (2015).
• [22] Hoang H.N., Nagashima Y., Mori S., Kagechika H. and Matsuda T., “CO2-expanded bio-based liquids as novel solvents for enantioselective biocatalysis”, Tetrahedron, 73: 2984-2989, (2017). [23] Khandelwal S., Tailor Y.K. and Kumar M., “Deep eutectic solvents (DESs) as eco-friendly and sustainable solvent/catalyst systems in organic transformations”, Journal of Molecular Liquids, 215: 345-386, (2016).
• [24] Belafriekh A., Secundo F., Serra S. and Djeghaba Z., “Enantioselective enzymatic resolution of racemic alcohols by lipases in green organic solvents”, Tetrahedron : Asymmetry, 28: 473-478, (2017).
• [25] Xia C.G., Wu X.M., Sun W. and Xin J.Y., “Lipase catalyzed kinetic resolution of secondary alcohols with improved enantioselectivity in propylene carbonate”, World J Microbiol Biotechnology, 24: 2421-2424, (2008). doi: 10.1007/s11274-008-9762-y.
• [26] Wu X., Zhu L.M., Branford-White C.J. and Xia C.G., “Propylene Carbonate as a Green Solvent for Kinetic Resolution of Secondary Alcohols Catalyzed by Candida antarctica Lipase”, 3rd International Conference on Bioinformatics and Biomedical Engineering, Beijing, 1-4, (2009). doi: 10.1109/ICBBE.2009.5163254.
• [27] Pyo S.H., Park J.H., Chang T.S. and Hatti-Kaul R., “Dimethyl carbonate as a green chemical”, Current Opinion in Green and Sustainable Chemistry,5: 61-66, (2017).
• [28] Ülger C. and Takaç S., “Kinetics of lipase-catalysed methyl gallate production in the presence of deep eutectic solvent”, Biocatalysis and Biotransformation, 35(6): 407-416, (2017).
• [29] Hara P., Mikkola J.P., Murzin D.Y. and Kanerva L.T., “Supported ionic liquids in Burkholderia cepacia lipase-catalyzed asymmetric acylation”, Journal of Molecular Catalysis B: Enzymatic, 67: 129-134, (2010). doi: 10.1016/j.molcatb.2010.07.018.
• [30] Rios A.P., Rantwijk F. and Sheldon R.A., “Effective resolution of 1-phenyl ethanol by Candida antarctica lipase B catalysed acylation with vinyl acetate in protic ionic liquids (PILs)”, Green Chemistry, 14: 1584-1588, (2012). doi: 10.1039/c2gc35196j.
• [31] Chen Z.G., Zhang D.N., Cao L. and Han Y.B., “Highly efficient and regioselective acylation of pharmacologically interesting cordycepin catalyzed by lipase in the eco-friendly solvent 2-methyltetrahydrofuran”, Bioresource Technology, 133: 82-86, (2013).
• [32] Espino M., Fernández M.Á, Gomez F.J.V. and Silva M.F., “Natural designer solvents for greening analytical chemistry”, Trends in Analytical Chemistry, 76: 126-136, (2016).
• [33] Shah S. and Gupta M.N., “Kinetic resolution of (±)1-phenylethanol in [Bmim][PF6] using high activity preparations of lipases”, Bioorganic & Medicinal Chemistry Letters, 17: 921-924, (2007). doi:10.1016/j.bmcl.2006.11.057.
• [34] Mohamed H.M., “Green, environment-friendly, analytical tools give insights in pharmaceuticals and cosmetics analysis”, Trends in Analytical Chemistry, 66: 176-192, (2015).
• [35] Hoyos P., Quezada M.A., Sinisterra J.V. and Alcántara A.R., “Optimised Dynamic Kinetic Resolution of benzoin by a chemoenzymatic approach in 2-MeTHF”, Journal of Molecular Catalysis B: Enzymatic, 72: 20-24, (2011).
• [36] Magadum D.B. and Yadav G.D., “Enantioselective resolution of (R,S)-α-methyl-4-pyridinemethanol using immobilized biocatalyst : Optimization and kinetic modeling”, Biochemical Engineering Journal, 122: 152-158, (2017).
• [37] Kirilin A., Sahin S., Mäki Arvela P., Wӓrnå J., Salmi T., Murzin D.Y., “Kinetics and Modeling of (R,S)-1-Phenylethanol Acylation over Lipase”, International Journal of Chemical Kinetics, 42 (10): 629-639, (2010). doi: 10.1002/kin.20504.
• [38] Fogler H.S., “Elements of Chemical Reaction Engineering”, 4, Pearson Education International, Massachusetts, (2008).
• [39] Goswami A. and Goswami J., “DMSO-triggered enhancement of enantioselectivity in Novozyme[435]-catalyzed transesterification of chiral 1-phenylethanols”, Tetrahedron Letters, 46: 4411-4413, (2005). doi:10.1016/j.tetlet.2005.03.147.
• [40] Zhou H., Chen J., Ye L., Lin H. and Yuan Y., “Enhanced performance of lipase-catalyzed kinetic resolution of secondary alcohols in monoether-functionalized ionic liquids”, Bioresource Technology, 102: 5562-5566, (2011).