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Candida antarctica Lipase B A Tool for the Preparation of Optically Active Alcohols

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Enzymes in Nonaqueous Solvents

Part of the book series: Methods in Biotechnology ((MIBT,volume 15))

Abstract

Lipases (E.C. 3.1.1.3) have proved to be efficient catalysts for the preparation of enantiomerically enriched compounds. Among them, Candida antarctica lipase B (CALB) has been found to be a particularly useful biocatalyst for the asymmetric transformation of sec-alcohols and related compounds. Indeed, about 200 compounds have already been successfully resolved using this enzyme. This number includes some chiral acids, but other lipases have proved to be superior to CALB for the resolution of most chiral acids. This chapter will, therefore, focus on the resolution of chiral alcohols. CALB is supplied as a recombinant protein patented by Novo-Nordisk. Despite its origin in the Antarctics, CALB is stable at 60-80°C for extended periods of time, once it is immobilized (1). Furthermore, CALB retains most of its activity and robustness in nonaqueous media. An example is that Glaxo selected CALB out of two lipases suitable for a multikilo resolution, because of its stability over multiple-use cycles in nonaqueous media (2).

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References

  1. Anderson, E. M., Larsson, K. M., and Kirk, O. (1998) One biocatalyst-many applications: the use of Candida antarctica B-lipase inorganic synthesis. Biocatal.Biotransform. 16, 181–204.

    Article  CAS  Google Scholar 

  2. Stead, P., Marley, H., Mahmoudian, M., Webb, G., Noble, D., To Ip, Y., et al.(1996) Efficient procedures for the large-scale preparation of (1S,2S)-trans-2-methoxycyclohexanol, a key chiral intermediate in the synthesis of tricyclicβ-lactam antibiotics. Tetrahedron: Asymmetry 7, 2247–2250.

    Article  CAS  Google Scholar 

  3. Kazlauskas, R. J. and Bornscheuer, U. T. (1998) Biotransformations withlipases, inBiotechnology, 2nded., vol. 8a: Biotransformation I (Kelly, D. R., ed.), Wiley-VHC, Weinheim, pp. 37–191.

    Google Scholar 

  4. Kazlauskas, R. J., Weissfloch, A. N. E., Rappaport, A. T., and Cuccia, L. A. (1991) A rule to predict which enantiomer of a secondary alcohol reacts faster in reactions catalyzed by cholesterol esterase, Pseudomonas cepacia and Candida rugosa lipase. J. Org. Chem. 56, 2656–2665.

    Article  CAS  Google Scholar 

  5. Overbeeke, T., Ottosson, J., Hult, K., Jongejan, J., and Duine, J. (1999) The temperature dependence of enzymatic kinetic resolutions reveals the relative contribution of enthalpy and entropy to enzymatic enantioselectivity. Biocatal. Biotransform. 17, 61–79.

    Article  CAS  Google Scholar 

  6. Rotticci, D., Orrenius, C., Hult, K., and Norin, T. (1997) Enantiomerically enriched bifunctional sec-alcohols prepared by Candida antarctica lipase B catalysis. Evidence of non-steric interactions. Tetrahedron: Asymmetry 8, 359–362.

    Article  CAS  Google Scholar 

  7. Uenishi, J. I., Hiraoka, T., Hata, S., Nishiwaki, K., Yonemitsu, O., Nakamura, K., et al. (1998) Chiral pyridines:optical resolution of 1-(2-pyridyl)-and 1-[6-(2,2′-bipyridyl)]ethanols by lipase-catalyzed enantioselective acetylation. J. Org Chem. 63, 2481–2487.

    Article  CAS  Google Scholar 

  8. Kano, K., Negi, S., Kawashima, A., and Nakamura, K. (1997) Optical resolution of 1-arylethanols using transesterification catalyzed by lipases. Enantiomer 2, 261–266.

    CAS  Google Scholar 

  9. Ema, T., Jittani, M., Sazkai, T., and Utaka, M. (1998) Lipase-catalyzed kinetic resolution of large secondary alcohols having tetraphenylporphyrin. Tetrahedron Lett. 39, 6311–6314.

    Article  CAS  Google Scholar 

  10. Orrenius, C., Hæffner, F., Rotticci, D., Öhrner, N., Norin, T., and Hult, K. (1998) Chiral recognition of alcohol enantiomers in acyl transfer reactions catalysed by Candida antarctica lipase B. Biocatal. Biotransform. 16, 1–15.

    Article  CAS  Google Scholar 

  11. Johnson, C. R. and Sakaguchi, H. (1992) Enantioselective transesterifications using immobilized, recombinant Candida antarctica lipase B: resolution of 2-iodo-2-cycloalken-1-ols. Synlett 10, 813–816.

    Article  Google Scholar 

  12. Forro, E., Kanerva, L. T., and Fulop, F. (1998) Lipase-catalyzed resolution o 2-dialkylaminomethylcyclohexanols. Tetrahedron: Asymmetry 9, 513–520.

    Article  CAS  Google Scholar 

  13. Mulvihill, M. J., Gage, J. L., and Miller, M. J. (1998) Enzymic resolution of aminocyclopentenols as precursors to D-and L-carbocyclic nucleosides. J. Org. Chem. 63, 3357–3363.

    Article  CAS  Google Scholar 

  14. Curran, T. T. and Hay, D. A. (1996) Enzymic resolution of cis-4-O-TBS-2-cyclopenten-1,4-diol. Tetrahedron: Asymmetry 7, 2791,2792.

    Article  Google Scholar 

  15. Mitrochkine, A., Gil, G., and Réglier, M. (1995) Synthesis of enantiomerically pure cis and trans-2-amino-1-indanol. Tetrahedron: Asymmetry 6, 1535–1538.

    Article  CAS  Google Scholar 

  16. Igarashi, Y., Otsutomo, S., Harada, M., Nakano, S., and Watanabe, S. (1997) Lipase-mediated resolution of indene bromohydrin. Synthesis 5, 549–552.

    Google Scholar 

  17. Saksena, A. K., Girijavallabhan, V. M., Lovey, R. G., Pike, R. E., Wang, H., Ganguly, A. K., et al. (1995) Highly stereoselective access to novel 2,2,4-trisubstituted tetrahydrofurans by halocyclization: practical chemoenzymic synthesis of SCH 51048, a broad-spectrum orally active antifungal agent. Tetrahedron Lett. 36, 1787–1790.

    Article  CAS  Google Scholar 

  18. Johnson, C. R. and Bis, S. J. (1992) Enzymic asymmetrization of meso-2-cycloalken-1,4-diols and their diacetates in organic and aqueous media. Tetrahedron Lett. 33, 7287–7290.

    Article  CAS  Google Scholar 

  19. Chenevert, R. and Rose, Y. S. (1998) A chemoenzymic synthesis of both enantiomers of a cis-lignan lactone. Tetrahedron: Asymmetry 9, 2827–2831.

    Article  CAS  Google Scholar 

  20. Hof, R. P. and Kellogg, R. M. (1996) Synthesis and lipase-catalyzed resolution of 5-(hydroxymethyl)-1,3-dioxolan-4-ones: masked glycerol analogs as potential building blocks for pharmaceuticals. J. Org. Chem. 61, 3423–3427.

    Article  CAS  Google Scholar 

  21. Gais, H.-J. and von der Weiden, I. (1996) Preparation of enantiomerically pure α-hydroxymethyl S-tert-butyl sulfones by Candida antarctica lipase catalyzed resolution. Tetrahedron: Asymmetry 7, 1253–1256.

    Article  CAS  Google Scholar 

  22. Patti, A., Lambusta, D., Piattelli, M., Nicolosi, G., McArdle, P., Cunningham, D., et al. (1997) Lipase-assisted preparation of enantiopure ferrocenyl sulfides possessing planar chirality and their use in the synthesis of chiral sulfoxides. Tetrahedron 53, 1361–1368.

    Article  CAS  Google Scholar 

  23. Tanaka, K., Osuga, H., Suzuki, H., Shogase, Y., and Kitahara, Y. (1998) Synthesis, enzymic resolution and enantiomeric enhancement of bis(hydroxy-methyl)[7]thiaheterohelicenes. J. Chem. Soc., Perkin Trans. 1 5, 935–940.

    Article  Google Scholar 

  24. Adam, W., Groer, P., and Saha-Möller, C. (1997) Enzyme preparation of optically active α-methylene β-lactone by lipase-catalyzed kinetic resolution through asymmetric transesterification. Tetrahedron: Asymmetry 8, 833–836.

    Article  CAS  Google Scholar 

  25. Pozo, M. and Gotor, V. (1993) Kinetic resolution of vinyl carbonates through a lipase-mediated synthesis of their carbonate and carbamate derivatives. Tetrahedron 49, 10,725–10,732.

    Article  CAS  Google Scholar 

  26. Parker, M.-C., Brown, S. A., Robertson, L., and Turner, N. J. (1998) Enhancement of Candida antarctica lipase B enantio selectivity and activity in organic solvents. J. Chem. Soc. Chem. Commun. 2247,2248.

    Google Scholar 

  27. Wang, Y.-F., Lalonde, J. J., Momongan, M., Bergbreiter, D., E., and Wong, C.-H. (1988) Lipase-catalyzed irreversible transesterifications using enol esters as acylating reagents: preparative syntheses of alcohols, glycerol derivatives, sugars, and organometallics. J. Am. Chem. Soc. 110, 7200–7205.

    Article  CAS  Google Scholar 

  28. Weber, H. K., Stecher, H., and Faber, K. (1995) Sensitivity of microbial lipases to acetaldehyde formed by acyl-transfer reactions from vinyl esters. Biotechnol. Lett. 17, 803–808.

    Article  CAS  Google Scholar 

  29. Frykman, H., Öhrner, N., Norin, T., and Hult, K. (1993) S-Ethyl thiooctanoate as acyl donor in lipase catalysed resolution of secondary alcohols. Tetrahedron Lett. 34, 1367–1300.

    Article  CAS  Google Scholar 

  30. Trollsås, M., Orrenius, C., Sahlen, F., Gedde, U. W., Norin, T., Hult, A., et al. (1996) Preparation of a novel cross-linked polymer for second-order nonlinear optics. J. Am. Chem. Soc. 118, 8542–8548.

    Article  Google Scholar 

  31. Öhrner, N., Martinelle, M., Mattson, A., Norin, T., and Hult, K. (1992) Displacement of the equilibrium in lipase catalyzed transesterification in ethyl octanoate by continuous evaporation of ethanol. Biotechnol. Lett. 14, 263–268.

    Article  Google Scholar 

  32. Bianchi, D., Cesti, P., and Battistel, E. (1988) Anhydrides as acylating agents in lipase-catalyzed stereo selective esterification of racemic alcohols. J. Org. Chem. 53, 5531–5534.

    Article  CAS  Google Scholar 

  33. Rakels, J. L. L., Straathof, A. J. J., and Heijnen, J. J. (1993) A simple method to determine the enantiomeric ratio in enantioselective biocatalysis. EnzymeMicrob. Technol. 15, 1051–1056.

    Article  CAS  Google Scholar 

  34. Reslow, M., Adlercreutz, P., and Mattiasson, B. (1987) Organic solvents forbioorganic synthesis 1. Optimization of parameters for a chymotrypsin catalyzed process. Appl. Microbiol. Biotechnol. 26, 1–8.

    Article  CAS  Google Scholar 

  35. Martinelle, M. and Hult, K. (1995) Kinetics of acyl transfer reactions in organic media catalysed by Candida antarctica lipase B. Biochim. Biophys. Acta 1251, 191–197.

    Article  Google Scholar 

  36. Orrenius, C., Norin, T., Hult, K., and Carrea, G. (1995) The Candida antarctica lipase B catalyzed kinetic resolution of seudenol in non-aqueous media of controlled water activity. Tetrahedron: Asymmetry 6, 3023–3030.

    Article  CAS  Google Scholar 

  37. Iglesias, L., Sanchez, V., Rebolledo, F., and Gotor, V. (1997) Candida antarctica B lipase catalysed resolution of 1-(heteroaryl)ethylamines. Tetrahedron: Asymmetry 8, 2675–2677.

    Article  CAS  Google Scholar 

  38. Arroyo, M. and Sinisterra, J. V. (1995) Influence of chiral carvones on selectivity of pure lipase-B from Candida antarctica. Biotechnol. Lett. 17, 525–530.

    Article  CAS  Google Scholar 

  39. Morrone, R., Nicolosi, G., Patti, A., and Piattelli, M. (1995) Resolution of racemic flurbiprofen by lipase-mediated esterification in organic solvent. Tetrahedron: Asymmetry 6, 1773–1778.

    Article  CAS  Google Scholar 

  40. Roure, F., Ducret, A., Trani, M., and Lortie, R. (1997) Enantioselective esterification of racemic ibuprofen in solvent media under reduced pressure. J. Chem. Technol. Biotechnol. 69, 266–270.

    Article  CAS  Google Scholar 

  41. Morrone, R., Nicolosi, G., and Patti, A. (1997) Resolution of racemic 1-hydroxyalkylferrocenes by lipase B from Candida antarctica. Gazz. Chim. Ital. 127, 5–9.

    CAS  Google Scholar 

  42. Ducret, A., Pepin, P., Trani, M., and Lortie, R. (1996) Lipase-catalyzed selective esterification of ibuprofen. Ann. NYAcad. Sci. 799, 747–751.

    Article  CAS  Google Scholar 

  43. Kitaguchi, H., Itoh, I., and Ono, M. (1990) Effects of water and water-mimicking solvents on the lipase-catalyzed esterification in an apolar solvent. Chem. Lett. 1203–1206.

    Google Scholar 

  44. Högberg, H.-E., Edlund, H., Berglund, P., and Hedenström, H. (1993) Water activity influences enantioselectivity in a lipase-catalysed resolution by esterification in an organic solvent. Tetrahedron: Asymmetry 4, 2123–2126.

    Article  Google Scholar 

  45. Bodnár, J., Gubicza, L., and Szabó, L.-P. (1990) Enantiomeric separation of 2-chloropropionic acid by enzymatic esterification in organic solvents. J. Mol. Catal. 61, 353–361.

    Article  Google Scholar 

  46. Bovara, R., Carrea, G., Ottolina, G., and Riva, S. (1993) Water activity does not influence the enantioselectivity of lipase PS and lipoprotein lipase in organic solvents. Biotechnol. Lett. 15, 169–174.

    Article  Google Scholar 

  47. Wehtje, E., Costes, D., and Adlercreutz, P. (1997) Enantioselectivity of lipases: effects of water activity. J. Mol. Catal. B: Enzym. 3, 221–230.

    Article  CAS  Google Scholar 

  48. Chen, C.-S., Fujimoto, Y., Girdaukas, G., and Sih, C. J. (1982) Quantitative analysis of biochemical kinetic resolutions of enantiomers. J Am Chem. Soc. 104, 7294–7299.

    Article  CAS  Google Scholar 

  49. Heinsman, N. W. J. T., Orrenius, S. C., Marcelis, C. L. M., De Sousa Teixeira, A., Franssen, M. C. R., Van Der Padt, A., et al. (1998) Lipase mediated resolution of γ-branched chain fatty acid methyl esters. Biocatal. Biotransform. 16, 145–162.

    Article  CAS  Google Scholar 

  50. Schieweck, F. and Altenbach, H.-J. (1998) Preparation of S-(-)-2-acetoxymethyl-2,5-dihydrofuran and S-(-)-N-Boc-2-hydroxymethyl-2,5-dihydropyrrole by enzymatic resolution. Tetrahedron: Asymmetry 9, 403–406.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Chemistry and Organic Chemistry, Royal Institute of Technology, Stockholm, Sweden

    Didier Rotticci & Torbjörn Norin

  2. Department of Biotechnology, Royal Institute of Technology, Stockholm, Sweden

    Jenny Ottosson & Karl Hult

Authors
  1. Didier Rotticci
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  2. Jenny Ottosson
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  3. Torbjörn Norin
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  4. Karl Hult
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Editor information

Editors and Affiliations

  1. Institute of Food Research, Norwich, UK

    Evgeny N. Vulfson

  2. University of Strathclyde, Glasgow, UK

    Peter J. Halling

  3. Brock University, St. Catharines, Ontario, Canada

    Herbert L. Holland

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© 2001 Humana Press Inc.

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Rotticci, D., Ottosson, J., Norin, T., Hult, K. (2001). Candida antarctica Lipase B A Tool for the Preparation of Optically Active Alcohols. In: Vulfson, E.N., Halling, P.J., Holland, H.L. (eds) Enzymes in Nonaqueous Solvents. Methods in Biotechnology, vol 15. Humana Press. https://doi.org/10.1385/1-59259-112-4:261

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  • DOI: https://doi.org/10.1385/1-59259-112-4:261

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-929-2

  • Online ISBN: 978-1-59259-112-1

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