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Isomerase activity of Candida rugosa lipase in the optimized conversion of racemic ibuprofen to (S)-ibuprofen

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Abstract

The Candida rugosa lipase catalyzed Dynamic Kinetic Resolution of racemic ibuprofen methyl ester produced (S)-ibuprofen in over 90% yield within 72 h at pH 7.6. The best concentration of various buffers for these reactions ranged from 0.2 to 0.5 M. The commercial lipase was found to be acidic altering the final pH of the reaction mixtures. Dimethylformamide co-solvent maintained the reaction pH better than dimethylsulfoxide. Lower concentrations of ibuprofen methyl ester and higher stirring rates led to faster conversions. The minimal amount of lipase needed was 20 mg/mL buffer. Reaction of (R)-ibuprofen methyl ester under the optimized conditions excluding the lipase led to no racemization, indicating that the conversion of (R)-ibuprofen methyl ester to (S)-ibuprofen is catalyzed by the enzyme, thus, indicating Candida rugosa lipase possess Isomerase activity.

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References

  1. Persson, B. A., A. L. Larsson, M. Le Ray, and J. Bäckvall (1999) Ruthenium-and enzyme-catalyzed dynamic kinetic resolution of secondary alcohols. J. Am. Chem. Soc. 121: 1645–1650.

    Article  CAS  Google Scholar 

  2. Do, Y., I. Hwang, M. Kim, and J. Park (2010) Photoactivated racemization catalyst for dynamic kinetic resolution of secondary alcohols. J. Org. Chem. 75: 5740–5742.

    Article  CAS  Google Scholar 

  3. Akai, S., R. Hanada, N. Fujiwara, Y. Kita, and M. Egi (2010) One-pot synthesis of optically active allyl esters via Lipasevanadium combo catalysis. Org. Lett. 12: 4900–4903.

    Article  CAS  Google Scholar 

  4. Deska, J., C. del Pozo Ochoa, and J. Bäckvall (2010) Chemoenzymatic dynamic kinetic resolution of axially chiral allenes. Chem. Eur. J. 16: 4447–4451.

    Article  CAS  Google Scholar 

  5. Kim, M., W. Kim, K. Han, Y. K. Choi, and J. Park (2007) Dynamic kinetic resolution of primary amines with a recyclable Pd nanocatalyst for racemization. Org. Lett. 9: 1157–1159.

    Article  Google Scholar 

  6. Stirling, M., J. Blacker, and M. I. Page (2007) Chemoenzymatic dynamic kinetic resolution of secondary amines. Tetrahedron Lett. 48: 1247–1250.

    Article  CAS  Google Scholar 

  7. Fransson, A. L., L. Borén, O. Pàmies, and J. Bäckvall (2005) Kinetic resolution and chemoenzymatic dynamic kinetic resolution of functionalized γ-hydroxy amides. J. Org. Chem. 70: 2582–2587.

    Article  CAS  Google Scholar 

  8. Baxter, S., S. Royer, G. Grogan, F. Brown, K. E. Holt-Tiffin, I. N. Taylor, I. G. Fotheringham, and D. J. Campopiano (2012) An improved racemase/acylase biotransformation for the preparation of enantiomerically pure amino acids. J. Am. Chem. Soc. 134: 19310–19313.

    Article  CAS  Google Scholar 

  9. Engström, K., M. Shakeri, and J. Bäckvall (2011) Dynamic kinetic resolution of ß-amino esters by a heterogeneous system of a palladium nanocatalyst and candida antarctica lipase A. Eur. J. Org. Chem. 10: 1827–1830.

    Article  Google Scholar 

  10. Rodríguez-Docampo, Z., C. Quigley, S. Tallon, and S. J. Connon (2012) The dynamic kinetic resolution of azlactones with thiol nucleophiles catalyzed by arylated, deoxygenated cinchona alkaloids. J. Org. Chem. 77: 2407–2414.

    Article  Google Scholar 

  11. Rodríguez, C., G. de Gonzalo, A. Rioz-Martínez, D. E. T. Pazmino, M. W. Fraaije, and V. Gotor (2010) BVMO-catalysed dynamic kinetic resolution of racemic benzyl ketones in the presence of anion exchange resins. Org. Bimol. Chem. 8: 1121–1125.

    Article  Google Scholar 

  12. Pamies, O. and J. Baeckvall (2002) Efficient lipase-catalyzed kinetic resolution and dynamic kinetic resolution of ß-hydroxy nitriles. correction of absolute configuration and transformation to chiral ß-hydroxy acids and γ-amino alcohols. Adv. Synth. Catal. 344: 947–952.

    CAS  Google Scholar 

  13. Kiełbasiński, P., M. Rachwalski, M. Miko ajczyk, M. A. Moelands, B. Zwanenburg, and F. P. Rutjes (2005) Lipase-promoted dynamic kinetic resolution of racemic ß-hydroxyalkyl sulfones. Tetrahedron: Asymm. 16: 2157–2160.

    Article  Google Scholar 

  14. Shiina, I., K. Ono, and K. Nakata (2012) Non-enzymatic dynamic kinetic resolution of racemic a-arylalkanoic acids: An advanced asymmetric synthesis of chiral nonsteroidal antiinflammatory drugs (NSAIDs). Catal. Sci. Tech. 2: 2200–2205.

    Article  CAS  Google Scholar 

  15. Ng, I. and S. Tsai (2006) Characterization and application of Carica papaya lipase to the dynamic kinetic resolution of (R,S)-naproxen thioester. J. Chin. Inst. Chem. Eng. 37: 375–382.

    CAS  Google Scholar 

  16. Yuchun, X., L. Huizhou, and C. Jiayong (2000) Kinetics of base catalyzed racemization of ibuprofen enantiomers. Int. J. Pharm. 196: 21–26.

    Article  CAS  Google Scholar 

  17. Liu, Y., F. Wang, and T. Tan (2009) Cyclic resolution of racemic ibuprofen via coupled efficient lipase and acid/base catalysis. Chirality 21: 349–353.

    Article  CAS  Google Scholar 

  18. Xin, J., Y. Zhao, Y. Shi, C. Xia, and S. Li (2005) Lipase-catalyzed naproxen methyl ester hydrolysis in water-saturated ionic liquid: significantly enhanced enantioselectivity and stability. J. Microbiol. Biotechnol. 21: 193–199.

    Article  CAS  Google Scholar 

  19. Fazlena, H., A. Kamaruddin, and M. Zulkali (2006) Dynamic kinetic resolution: alternative approach in optimizing S-ibuprofen production. Bioproc. Biosyst. Eng. 28: 227–233.

    Article  CAS  Google Scholar 

  20. Chavez-Flores, D. and J. M. Salvador (2012) Facile conversion of racemic ibuprofen to (S)-ibuprofen. Tetrahedron: Asym. 23:237–239.

    Article  CAS  Google Scholar 

  21. Lin, H. and S. Tsai (2003) Dynamic kinetic resolution of (R,S)-naproxen 2, 2, 2-trifluoroethyl ester via lipase-catalyzed hydrolysis in micro-aqueous isooctane. J. Mol. Catal. B: Enz. 24-25: 111–120.

    Article  CAS  Google Scholar 

  22. Xin, J., S. Li, Y. Xu, J. Chui, and C. Xia (2001) Dynamic enzymatic resolution of naproxen methyl ester in a membrane bioreactor. J. Chem. Technol. Biotechnol. 76: 579–585.

    Article  CAS  Google Scholar 

  23. Chang, C., S. Tsai, and J. Kuo (1999) Lipase-catalyzed dynamic resolution of naproxen 2, 2, 2-trifluoroethyl thioester by hydrolysis in isooctane. Biotechnol. Bioeng. 64: 120–126.

    Article  CAS  Google Scholar 

  24. Chen, C., Y. Cheng, and S. Tsai (2002) Lipase-catalyzed dynamic kinetic resolution of (R, S)-fenoprofen thioester in isooctane. J. Chem. Technol. Biotechnol. 77:699–705.

    Article  CAS  Google Scholar 

  25. Lin, C. and S. Tsai (2000) Dynamic kinetic resolution of suprofen thioester via coupled trioctylamine and lipase catalysis. Biotechnol. Bioeng. 69: 31–38.

    Article  CAS  Google Scholar 

  26. Ong, A. L., A. H. Kamaruddin, and S. Bhatia (2005) Current technologies for the production of (S)-ketoprofen: Process perspective. Process Biochem. 40:3526–3535.

    Article  CAS  Google Scholar 

  27. Chavez-Flores, D. and J. M. Salvador (2009) Commercially viable resolution of ibuprofen. Biotechnol. J. 4: 1222–1224.

    Article  CAS  Google Scholar 

  28. Yamaji, T., T. Saito, K. Hayamizu, M. Yanagisawa, and O. Yamamoto Spectral Database for Organic Compounds SDBS. Http://Sdbs.Db.Aist.Go.Jp. http://sdbs.db.aist.go.jp

  29. Koul, S., J. L. Koul, B. Singh, M. Kapoor, R. Parshad, K. S. Manhas, S. C. Taneja, and G. N. Qazi (2005) Trichosporon beigelli esterase (TBE): A versatile esterase for the resolution of economically important racemates. Tetrahedron: Asymm. 16: 2575–2591.

    Article  CAS  Google Scholar 

  30. Takaç, S. and D. Mutlu (2007) A parametric study on biphasic medium conditions for the enantioselective production of naproxen by Candida rugosa lipase. Appl. Biochem. Biotechnol. 141: 15–26.

    Article  Google Scholar 

  31. Mathews, A. (1909) The spontaneous oxidation of the sugars. J. Biol. Chem. 6: 3–20.

    CAS  Google Scholar 

  32. Hardegger, E., K. Kreis, and H. E. Khadem (1952) Oxidation of several mono-and disaccharides with alkali and oxygen. Helv. Chim. Acta 35: 618–623.

    Article  CAS  Google Scholar 

  33. Good, N. E., G. D. Winget, W. Winter, T. N. Connolly, S. Izawa, and R. M. Singh (1966) Hydrogen ion buffers for biological research. Biochem. 5: 467–477.

    Article  CAS  Google Scholar 

  34. Doonan, S. (2004) Making and changing buffers. Methods Mol. Biol. 244: 91–99.

    CAS  Google Scholar 

  35. Steenkamp, L. and D. Brady (2008) Optimisation of stabilised Carboxylesterase NP for enantioselective hydrolysis of naproxen methyl ester. Proc. Biochem. 43: 1419–1426.

    Article  CAS  Google Scholar 

  36. Liu, X., J. Xu, J. Pan, and J. Zhao (2010) Efficient production of (S)-Naproxen with (R)-substrate recycling using an overexpressed carboxylesterase BsE-NP01. Appl. Biochem. Biotechnol. 162: 1574–1584.

    Article  CAS  Google Scholar 

  37. Quax, W. and C. Broekhuizen (1994) Development of a newBacillus carboxyl esterase for use in the resolution of chiral drugs. Appl. Microbiol. Biotechnol. 41: 425–431.

    CAS  Google Scholar 

  38. Gonawan, F. N., L. S. Yon, A. H. Kamaruddin, and M. H. Uzir (2012) Effect of co-solvent addition on the reaction kinetics of the lipase-catalyzed resolution of ibuprofen ester. J. Chem. Technol. Biotechnol. 88: 672–679.

    Article  Google Scholar 

  39. Lee, W. H., K. Kim, M. G. Kim, and S. B. Lee (1995) Enzymatic resolution of racemic ibuprofen esters: Effects of organic cosolvents and temperature. J. Ferment. Bioeng. 80: 613–615.

    Article  CAS  Google Scholar 

  40. Qu, X., A. Allan, G. Chui, T. J. Hutchings, P. Jiao, L. Johnson, W. Y. Leung, P. K. Li, G. R. Steel, and A. S. Thompson (2013) Hydrolysis of ibuprofenoyl-CoA and other 2-APA-CoA esters by human acyl-CoA thioesterases-1 and-2 and their possible role in the chiral inversion of profens. Biochem. Pharmacol. 86: 1621–1625.

    Article  CAS  Google Scholar 

  41. Woodman, T. J., P. J. Wood, A. S. Thompson, T. J. Hutchings, G. R. Steel, P. Jiao, M. D. Threadgill, and M. D. Lloyd (2011) Chiral inversion of 2-arylpropionyl-CoA esters by human a-methylacyl-CoA racemase 1A (P504S)-a potential mechanism for the anti-cancer effects of ibuprofen. Chem. Commun. 47: 7332–7334.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, University of Texas at El Paso, El Paso, TX, 79968, USA

    Saideh S. Mortazavi & James M. Salvador

  2. Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, 31125, Mexico

    David Chavez-Flores

Authors
  1. Saideh S. Mortazavi
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  2. David Chavez-Flores
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  3. James M. Salvador
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Correspondence to James M. Salvador.

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Mortazavi, S.S., Chavez-Flores, D. & Salvador, J.M. Isomerase activity of Candida rugosa lipase in the optimized conversion of racemic ibuprofen to (S)-ibuprofen. Biotechnol Bioproc E 21, 634–640 (2016). https://doi.org/10.1007/s12257-016-0231-4

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